MAPT

MAPT
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1I8H, 4GLR, 2ON9, 3OVL, 4E0M, 4E0N, 4E0O, 4FL5, 4NP8, 2MZ7, 4TQE, 4Y5I, 4Y32, 5DMG, 4Y3B, 5HF3, 5E2W, 5E2V
Identifikatori
Aliasi	MAPT
Vanjski ID-jevi	OMIM: 157140 MGI: 97180 HomoloGene: 74962 GeneCards: MAPT
Lokacija gena (čovjek)
Hrom.	Hromosom 17 (čovjek)
Kraj	46,028,334 bp
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
Kraj	104,332,090 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• apolipoprotein binding; • SH3 domain binding; • vezivanje tubulina; • GO:0001948, GO:0016582 vezivanje za proteine; • lipoprotein particle binding; • vezivanje enzima; • vezivanje sa DNK; • actin binding; • microtubule binding; • dynactin binding; • receptor ligand activity; • protein phosphatase 2A binding; • Hsp90 protein binding; • minor groove of adenine-thymine-rich DNA binding; • double-stranded DNA binding; • single-stranded DNA binding; • vezivanje sa RNK; • protein kinase binding; • protein-macromolecule adaptor activity; • phosphatidylinositol binding; • vezivanje identičnih proteina; • protein homodimerization activity; • sequence-specific DNA binding; • chaperone binding; • histone-dependent DNA binding; • microtubule lateral binding; • phosphatidylinositol bisphosphate binding;
Ćelijska komponenta	• citoplazma; • cell body; • projekcija ćelije; • nuclear periphery; • growth cone; • neurofibrillary tangle; • ćelijska membrana; • tubulin complex; • dendrit; • cytoplasmic ribonucleoprotein granule; • citoskelet; • jedro; • citosol; • Mikrotubula; • microtubule associated complex; • membrana; • nuclear speck; • Akson; • somatodendritic compartment; • soma; • axon cytoplasm; • extracellular region; • intracellular anatomical structure; • mitohondrija; • microtubule cytoskeleton; • axolemma; • neuron projection; • dendritična kičma; • main axon; • Lipidni splav; • glial cell projection;
Biološki proces	• generation of neurons; • regulation of autophagy; • regulation of microtubule polymerization; • positive regulation of microtubule polymerization; • positive regulation of axon extension; • microtubule cytoskeleton organization; • microglial cell activation; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • GO:0072468 Transdukcija signala; • Memorija; • negative regulation of mitochondrial membrane potential; • axonal transport of mitochondrion; • cytoplasmic microtubule organization; • neuron projection development; • positive regulation of superoxide anion generation; • negative regulation of kinase activity; • cellular response to heat; • astrocyte activation; • intracellular distribution of mitochondria; • synapse organization; • regulation of calcium-mediated signaling; • protein complex oligomerization; • plus-end-directed organelle transport along microtubule; • regulation of mitochondrial fission; • negative regulation of mitochondrial fission; • axonal transport; • regulation of cellular response to heat; • positive regulation of neuron death; • positive regulation of protein localization to synapse; • neurofibrillary tangle assembly; • negative regulation of establishment of protein localization to mitochondrion; • positive regulation of diacylglycerol kinase activity; • regulation of response to DNA damage stimulus; • internal protein amino acid acetylation; • cell-cell signaling; • response to lead ion; • regulation of signaling receptor activity; • negative regulation of gene expression; • rRNA metabolic process; • central nervous system neuron development; • regulation of microtubule polymerization or depolymerization; • regulation of chromosome organization; • stress granule assembly; • GO:0072353 cellular response to reactive oxygen species; • microtubule polymerization; • regulation of synaptic plasticity; • axon development; • regulation of microtubule cytoskeleton organization; • supramolecular fiber organization; • regulation of long-term synaptic depression; • positive regulation of protein localization; • negative regulation of tubulin deacetylation; • amyloid fibril formation; • cellular response to nerve growth factor stimulus; • cellular response to brain-derived neurotrophic factor stimulus;
	Izvori:Amigo / QuickGO
Ortolozi
	4137
	17762
	ENSG00000186868; ENSG00000276155; ENSG00000277956
	ENSMUSG00000018411
	P10636
	P10637
NM_001123066; NM_001123067; NM_001203251; NM_001203252; NM_005910;
	NM_016834; NM_016835; NM_016841; NM_001377265; NM_001377266; NM_001377267; NM_001377268
	NM_001038609; NM_010838; NM_001285454; NM_001285455; NM_001285456
NP_001116538; NP_001116539; NP_001190180; NP_001190181; NP_005901;
	NP_058518; NP_058519; NP_058525; NP_001364194; NP_001364195; NP_001364196; NP_001364197
NP_001033698; NP_001272383; NP_001272384; NP_001272385; NP_034968;
	NP_001390904; NP_001390905; NP_001390906; NP_001390907; NP_001390908; NP_001390909; NP_001390910; NP_001390911; NP_001390912; NP_001390913; NP_001390916; NP_001390919; NP_001390921; NP_001390923; NP_001390925; NP_001390927; NP_001390928; NP_001390931; NP_001390933; NP_001390934; NP_001390935; NP_001390939; NP_001390940; NP_001390941; NP_001390943; NP_001390944; NP_001390945
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Tau proteini (ili τ proteini, prema grčkom slovu koje označava ovo ime) su grupa od šest visoko rastvorljivih proteinskih izoformi proizvedenih alternativnom preradom primarnog transkripta gena MAPT (mikrotubulski-asocirani protein tau).^[5]^[6] Prvenstvenu ulogu imaju u održavanju stabilnosti mikrotubula u aksonima i obiluju neuronima centralnog nervnog sistema (CNS). Manje su česti drugdje, ali se također eksprimiraju na vrlo niskim nivoima u CNS-ovim astrocitima i oligodendrocitima .^[7]

Povezani sa tau proteinima koji su odgovorni za patološka stanje i demencija nervnog sistema, kao što su Alzheimerova i Parkinsonova bolest^[8] Tau proteini postali su hiperfosforilirani nerastvorljivi agregati zvani neurofibrilskii sklopovi. Proteini tau identificirani su 1975. godine, kao termički stabilni proteini, neophodni za sastavljanje mikrotubula^[9]^[10] > i od tada su okarakterizirani kao suštinski poremećeni proteini.^[11]

Funkcija

Stabilizacija mikrotubula

Kod ljudi, tau proteini se češće nalaze u neuronima nego u neneuronskim ćelijama. Jedna od glavnih funkcija tau-a je moduliranje stabilnosti aksonskih mikrotubula.^[10]^[12] Ostali sustemski proteini povezani sa mikrotubulama (MAP) mogu obavljati slične funkcije, kao što je predloženu u eksperimentu sa tau nokaut-miševima, koji nisu pokazali abnormalnosti u razvoju mozga – moguće zbog kompenzacije nedostatka tau od strane drugih MAP-ova.^[13]^[14]^[15]

Iako je tau prisutan u dendritima na niskim nivoima, gdje je uključen u postsinapsne skele,^[16] aktivan je prvenstveno u distalnim dijelovima aksona, gdje pruža stabilizaciju mikrotubula, ali i fleksibilnost po potrebi. Tau proteini komuniciraju s tubulinom, kako bi stabilizirali mikrotubule i u njima promovirali skupljanje tubulina.^[10] Tau ima dva načina za kontrolu stabilnosti mikrotubula: izoforme i fosforilacija.

Pored funkcije u stabilizaciji mikrotubula, utvrđeno je da Tau regrutuje signalne proteine i regulira aksonski transport posredovan mikrotubulama.^[17]

Translacija proteina

Tau je negativni regulator translacije proteina i u Drosophila ^[12] i moždanoj gangliji kod ljudi.^[18] Njegovo vezanje za ribosome, rezultira oštećenjem ribosomske funkcije, smanjenjem sinteza proteina i promijenjenom u funkciji funkciji sinapsi.^[12]^[18] Tau specifično komunicira s nekoliko ribosomskih proteina, uključujući presudni regulator translacije rpS6.^[19]

Ponašanje

Primarna nećelijska funkcija tau-a je negativna reguliranje dugoročnog pamćenja^[12] i olakšavanje navikavanja (oblik neasocijativnog učenja),^[12] dvije više i integrirane fiziološke funkcije. Budući da je regulacija tau-a presudna za pamćenje, ovo bi moglo objasniti vezu između tauopatija i kognitivnih oštećenja.

Kod miševa, dok su prijavljeni sojevi nokaut-sojevi bez otvorenog fenotipa u mladosti,^[13]^[20]^[21] kad ostare, pokazuju određenu mišićnu slabost, hiperaktivnost i oštećenje uslovljavanja straha.^[22] Međutim, ni prostorno učenje kod miševa,^[22]^[23]^[24] ni na kratkotrajnu memoriju (učenje) u Drosophila^[12] izgleda da ne utiče odsustvo tau-a.

Pored toga, tau nokaut-miševi imaju abnormalan ciklus spavanja i budnosti, s povećanim periodima budnosti i smanjenim nebrzih pokreta oka (NREM) tokom spavanja.^[25]

Ostale funkcije

Ostale tipske funkcije tau uključuju ćelijsku signalizaciju, razvoj neurona, neurozaštitu i apoptozu.^[14] Netipske, nestandardne uloge taua ^[26] su također pod aktuelnim istraživanjem, kao što je njihovo sudjelovanje u stabilnosti hromosoma, interakcija sa ćelijskim transkriptomom, interakcije s drugim citoskeletnim ili sinapsnim proteinima, uključenost u mijelinizaciju ili signalizacija u mozak za insulin, njegova uloga u izloženosti hroničnom stresu i depresiji, itd.

Genetika

U ljudi, MAPT gen za kodiranje tau proteina nalazi se na hromosomu 17, pozicija q21, koji sadrži 16 egzona.^[27] Glavni tau protein u ljudskom mozgu je kodiran iz 11 egzona. Egzoni 2, 3 i 10 su alternativno prerađeni u šest tau izoformi.^[28] U ljudskom mozgu, tau proteini čine porodicu od šest izoformi s rasponom od 352–441 aminokiselina. Tau izoforme su različite u nuli, jednom ili dva inserta od 29 aminokiselina na N-terminalnom dijelu (egzoni 2 i 3) i tri ili četiri regije ponavljanja na C-terminalnom dijelu (egzon 10). Dakle, najduža izoforma u CNS-u ima četiri ponavljanja (R1, R2, R3 i R4) i dva inserta (ukupno 441 aminokiselina), dok najkraća izoforma ima tri ponavljanja (R1, R3 i R4) i bez insercija (ukupno 352 aminokiseline).

Gen MAPT ima dvije haplogrupe, H1 i H2, u kojima se gen pojavljuje u obrnutim orijentacijama. Haplogrupa H2 česta je samo u Evropi i kod ljudi koji imaju evropsko porijeklo. Čini se da je haplogrupa H1 povezana s povećanom vjerovatnoćom određenih demencija, poput Alzheimerove bolesti. Prisustvo obje haplogrupe u Europi znači da rekombinacija između obrnutih haplotipova može rezultirati nedostatkom jedne od funkcionalnih kopija gena, što rezultira urođenim defektima.^[29]^[30]^[31]^[32]

Struktura

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 758 aminokiselina, a molekulska težina 78.928 Da.^[33].

10	20	30	40	50
MAEPRQEFEV	MEDHAGTYGL	GDRKDQGGYT	MHQDQEGDTD	AGLKESPLQT
PTEDGSEEPG	SETSDAKSTP	TAEDVTAPLV	DEGAPGKQAA	AQPHTEIPEG
TTAEEAGIGD	TPSLEDEAAG	HVTQEPESGK	VVQEGFLREP	GPPGLSHQLM
SGMPGAPLLP	EGPREATRQP	SGTGPEDTEG	GRHAPELLKH	QLLGDLHQEG
PPLKGAGGKE	RPGSKEEVDE	DRDVDESSPQ	DSPPSKASPA	QDGRPPQTAA
REATSIPGFP	AEGAIPLPVD	FLSKVSTEIP	ASEPDGPSVG	RAKGQDAPLE
FTFHVEITPN	VQKEQAHSEE	HLGRAAFPGA	PGEGPEARGP	SLGEDTKEAD
LPEPSEKQPA	AAPRGKPVSR	VPQLKARMVS	KSKDGTGSDD	KKAKTSTRSS
AKTLKNRPCL	SPKHPTPGSS	DPLIQPSSPA	VCPEPPSSPK	YVSSVTSRTG
SSGAKEMKLK	GADGKTKIAT	PRGAAPPGQK	GQANATRIPA	KTPPAPKTPP
SSGEPPKSGD	RSGYSSPGSP	GTPGSRSRTP	SLPTPPTREP	KKVAVVRTPP
KSPSSAKSRL	QTAPVPMPDL	KNVKSKIGST	ENLKHQPGGG	KVQIINKKLD
LSNVQSKCGS	KDNIKHVPGG	GSVQIVYKPV	DLSKVTSKCG	SLGNIHHKPG
GGQVEVKSEK	LDFKDRVQSK	IGSLDNITHV	PGGGNKKIET	HKLTFRENAK
AKTDHGAEIV	YKSPVVSGDT	SPRHLSNVSS	TGSIDMVDSP	QLATLADEVS
ASLAKQGL

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Umoždanom tkivu čovjeka ima šest tau izoformi i razlikuju se po broju veznih domena. Tri izoforme imaju po tri domena vezanja, a ostale tri po četiri. Vezujući domeni nalaze se na karboksi-kraju proteina i pozitivno su nabijeni (omogućavajući mu da se veže za negativno nabijenu mikrotubulu). Izoforme sa četiri vezujuća domena bolje stabilizuju mikrotubule od onih sa tri vezivna domena. Tau je fosfoprotein sa 79 potencijalnih mjesta fosforilacije serina (Ser) i treonina (Thr) na najdužoj tau izoformi. Fosforilacija u normalnim tau proteinima zabilježena je na približno 30 od ovih mjesta.^[34]

Fosforilaciju tau-a regulira mnoštvo kinaza, uključujući PKN, serin/treonin kinazu. Kada se PKN aktivira, fosforilira tau, što rezultira poremećajem organizacije mikrotubula.^[35] Fosforilacija tau-a je također i razvojno regulirana. Naprimjer, fetusni tau je jače fosforiliran u embrionskom CNS-u kod odraslih.^[36] Stepen fosforilacije u svih šest izoformi opada sa godinama usljed aktiviranja fosfataza.^[37] Poput kinaza, i fosfataze imaju ulogu u regulaciji fosforilacije tau-a. Naprimjer, PP2A i PP2B su prisutni u moždanom tkivu čovjeka i imaju sposobnost defosforilacije Ser396.^[38] Vezivanje ovih fosfataza za tau utiče na povezanost tau s mikrotubulama.

Predloženo je i da se fosforilacija tau-a regulira modifikacijom O - GlcNAc na različitim ostacima Ser i Thr.^[39]

Mehanizam

Akumulacija hiperfosforiliranog tau-a u neuronima povezana je sa neurofibrilnom degeneracijom.^[40] Stvarni mehanizam širenja tau iz jedne ćelije u drugu nije dobro identificiran. Također, ostali mehanizmi, uključujući oslobađanje tau-a i toksičnost, nisu jasni. Kao tau agregati, zamjenjuje tubulin, što zauzvrat pojačava fibrilizaciju tau-a.^[41] Predloženo je nekoliko metoda popagacije koje se javljaju sinapsnim kontaktom, kao što su proteini adhezije sinapanih ćelija, neuronska aktivnost i drugi sinapsnii i nesinapsni mehanizmi.^[42] Mehanizam tau agregacije još uvijek nije u potpunosti razjašnjen, ali nekoliko faktora favorizira ovaj proces, uključujući fosforilaciju tau-a i ione cinka.^[43]^[44]

Otpuštanje

Tau uključuje proces usvajanja i ispuštanja, koji je poznat kao sjetva. Za unos mehanizma tau proteina potrebno je prisustvo heparan-sulfat proteoglikana na ćelijskoj površini, gdje se događa makropinocitoza.^[45] S druge strane, oslobađanje tau-a ovisi o neuronskoj aktivnosti. Mnogi faktori utiču na oslobađanje tau, naprimjer, tip izoformi ili mutacije MAPT-a koje mijenjaju vanćelijski nivo tau-a.^[46] Prema Asaiju i njegovim kolegama, širenje tau proteina događa se iz entorinskog korteksa u hipokampusnu regiju, u ranim fazama bolesti. Također su sugerirali da je mikroglija također bila uključena u proces transporta, a njihova stvarna uloga još uvijek nije poznata.^[47]

Toksičnost

Toksične efekte, tau uzrokuje akumuliranjem unutar ćelija. U mehanizam toksičnosti uključeni su mnogi enzimi, kao što je PAR-1 kinaza. Ovaj enzim stimulira fosforilaciju serina 262 i 356, što zauzvrat dovodi do aktiviranja drugih kinaza (GSK-3 i CDK5), koje uzrokuju fosfoentropiju, povezanu sa bolešću.^[48] Na stupanj toksičnosti utiču različiti faktori, poput stupnja vezanja mikrotubula.^[49]^[50] Toksičnost bi se mogla dogoditi i neurofibrilarni splet s (NFT), što dovodi do ćelijske smrti i kognitivnog pada.

Klinički značaj

Hiperfosforilacija tau proteina (tau inkluzije, pTau) može rezultirati samosastavljanjem sklopa uparenih spiralnih i ravnih niti, koje su uključene u patogenezu Alzheimerove bolesti, čeonosljepoočne demencije i druge tauopatije.^[51] Svih šest tau izoforami prisutno je u često hiperfosforiliranom stanju u uparenim spiralnim nitima u mozgu osoba sa Alzheimerovom bolesti. U ostalim neurodegenerativnim bolestima zabilježeno je taloženje agregata obogaćenih određenim tau izoformama. Kada se pogrešno sklopi, ovaj inače vrlo rastvorljivi protein, može stvoriti izuzetno nerastvorljive agregate koji doprinose brojnim neurodegenerativnim bolestima. Tau protein ima direktan učinak na razgradnju živih ćelija uzrokovanu sklopovima koje formiraju i blokiraju sinapse živaca.^[52]

Rodno specifična ekspresija gena tau u različitim regijama ljudskog mozga nedavno je uključena u rodne razlike u manifestacijama i riziku od tauopatija.^[53] Neki aspekti funkcionisanja bolesti takođe ukazuju na to da ima neke sličnosti sa prionskim proteinima.^[54]

Interakcije

Dokazano je da protein tau komunicira sa:

Alfa-sinuklein,^[55]^[56]
FYN,^[57]
Proto-onkogen tirozin-protein kinaza Src
S100B,^[58]^[59] i
YWHAZ.^[60]

Također pogledajte

Tauopatija
Dementia pugilistica
Alzheimerova bolest
Primarna dobno vezana tauopatija
Tau astrogliopatija povezana sa starenjem
Kortikobazna degeneracija
Progresivna suprajedarna paraliza
Proteopatija
Pickova bolest
Čeonosljepoočna demencija i parkinsonizam povezani s hromosomom 17
Prion

Reference

^ ^a ^b ^c ENSG00000276155, ENSG00000277956 GRCh38: Ensembl release 89: ENSG00000186868, ENSG00000276155, ENSG00000277956 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000018411 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A (juni 1988). "Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau". Proceedings of the National Academy of Sciences of the United States of America. 85 (11): 4051–5. Bibcode:1988PNAS...85.4051G. doi:10.1073/pnas.85.11.4051. PMC 280359. PMID 3131773.
^ Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA (oktobar 1989). "Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease". Neuron. 3 (4): 519–26. doi:10.1016/0896-6273(89)90210-9. PMID 2484340. S2CID 19627629.
^ Shin RW, Iwaki T, Kitamoto T, Tateishi J (maj 1991). "Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues". Laboratory Investigation; A Journal of Technical Methods and Pathology. 64 (5): 693–702. PMID 1903170.
^ Lei P, Ayton S, Finkelstein DI, Adlard PA, Masters CL, Bush AI (novembar 2010). "Tau protein: relevance to Parkinson's disease". The International Journal of Biochemistry & Cell Biology. 42 (11): 1775–8. doi:10.1016/j.biocel.2010.07.016. PMID 20678581.
^ Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW (maj 1975). "A protein factor essential for microtubule assembly". Proceedings of the National Academy of Sciences of the United States of America. 72 (5): 1858–62. Bibcode:1975PNAS...72.1858W. doi:10.1073/pnas.72.5.1858. PMC 432646. PMID 1057175.
^ ^a ^b ^c Cleveland DW, Hwo SY, Kirschner MW (oktobar 1977). "Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin". Journal of Molecular Biology. 116 (2): 207–25. doi:10.1016/0022-2836(77)90213-3. PMID 599557.
^ Cleveland DW, Hwo SY, Kirschner MW (oktobar 1977). "Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly". Journal of Molecular Biology. 116 (2): 227–47. doi:10.1016/0022-2836(77)90214-5. PMID 146092.
^ ^a ^b ^c ^d ^e ^f Papanikolopoulou K, Roussou IG, Gouzi JY, Samiotaki M, Panayotou G, Turin L, Skoulakis EM (oktobar 2019). "Drosophila Tau Negatively Regulates Translation and Olfactory Long-Term Memory, But Facilitates Footshock Habituation and Cytoskeletal Homeostasis". The Journal of Neuroscience. 39 (42): 8315–8329. doi:10.1523/JNEUROSCI.0391-19.2019. PMC 6794924. PMID 31488613.
^ ^a ^b Harada A, Oguchi K, Okabe S, Kuno J, Terada S, Ohshima T, et al. (juni 1994). "Altered microtubule organization in small-calibre axons of mice lacking tau protein". Nature. 369 (6480): 488–91. Bibcode:1994Natur.369..488H. doi:10.1038/369488a0. PMID 8202139. S2CID 4322543.
^ ^a ^b Wang JZ, Liu F (juni 2008). "Microtubule-associated protein tau in development, degeneration and protection of neurons". Progress in Neurobiology. 85 (2): 148–75. doi:10.1016/j.pneurobio.2008.03.002. PMID 18448228. S2CID 32708424.
^ Ke YD, Suchowerska AK, van der Hoven J, De Silva DM, Wu CW, van Eersel J, et al. (juni 2012). "Lessons from tau-deficient mice". International Journal of Alzheimer's Disease. 2012 (873270): 873270. doi:10.1155/2012/873270. PMC 3375147. PMID 22720190.
^ Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, et al. (august 2010). "Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models". Cell. 142 (3): 387–97. doi:10.1016/j.cell.2010.06.036. PMID 20655099. S2CID 18776289.
^ Dehmelt L, Halpain S (2004). "The MAP2/Tau family of microtubule-associated proteins". Genome Biology. 6 (1): 204. doi:10.1186/gb-2004-6-1-204. PMC 549057. PMID 15642108.
^ ^a ^b Meier S, Bell M, Lyons DN, Rodriguez-Rivera J, Ingram A, Fontaine SN, et al. (januar 2016). "Pathological Tau Promotes Neuronal Damage by Impairing Ribosomal Function and Decreasing Protein Synthesis". The Journal of Neuroscience. 36 (3): 1001–7. doi:10.1523/JNEUROSCI.3029-15.2016. PMC 4719006. PMID 26791227.
^ Koren SA, Hamm MJ, Meier SE, Weiss BE, Nation GK, Chishti EA, et al. (april 2019). "Tau drives translational selectivity by interacting with ribosomal proteins". Acta Neuropathologica. 137 (4): 571–583. doi:10.1007/s00401-019-01970-9. PMC 6426815. PMID 30759285.
^ Dawson HN, Ferreira A, Eyster MV, Ghoshal N, Binder LI, Vitek MP (mart 2001). "Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice". Journal of Cell Science. 114 (Pt 6): 1179–87. doi:10.1242/jcs.114.6.1179. PMID 11228161.
^ Fujio K, Sato M, Uemura T, Sato T, Sato-Harada R, Harada A (juli 2007). "14-3-3 proteins and protein phosphatases are not reduced in tau-deficient mice". NeuroReport. 18 (10): 1049–52. doi:10.1097/WNR.0b013e32818b2a0b. PMID 17558294. S2CID 25235996.
^ ^a ^b Ikegami S, Harada A, Hirokawa N (februar 2000). "Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice". Neuroscience Letters. 279 (3): 129–32. doi:10.1016/s0304-3940(99)00964-7. PMID 10688046. S2CID 31204860.
^ Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, et al. (maj 2007). "Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model". Science. 316 (5825): 750–4. Bibcode:2007Sci...316..750R. doi:10.1126/science.1141736. PMID 17478722. S2CID 32771613.
^ Dawson HN, Cantillana V, Jansen M, Wang H, Vitek MP, Wilcock DM, et al. (august 2010). "Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease". Neuroscience. 169 (1): 516–31. doi:10.1016/j.neuroscience.2010.04.037. PMC 2900546. PMID 20434528.
^ Cantero JL, Hita-Yañez E, Moreno-Lopez B, Portillo F, Rubio A, Avila J (august 2010). "Tau protein role in sleep-wake cycle". Journal of Alzheimer's Disease. 21 (2): 411–21. doi:10.3233/JAD-2010-100285. PMID 20555133.
^ Sotiropoulos I, Galas MC, Silva JM, Skoulakis E, Wegmann S, Maina MB, et al. (novembar 2017). "Atypical, non-standard functions of the microtubule associated Tau protein". Acta Neuropathologica Communications. 5 (1): 91. doi:10.1186/s40478-017-0489-6. PMC 5707803. PMID 29187252.
^ Neve RL, Harris P, Kosik KS, Kurnit DM, Donlon TA (decembar 1986). "Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2". Brain Research. 387 (3): 271–80. doi:10.1016/0169-328x(86)90033-1. PMID 3103857.
^ Sergeant N, Delacourte A, Buée L (januar 2005). "Tau protein as a differential biomarker of tauopathies". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1739 (2–3): 179–97. doi:10.1016/j.bbadis.2004.06.020. PMID 15615637.
^ Shaw-Smith C, Pittman AM, Willatt L, Martin H, Rickman L, Gribble S, et al. (septembar 2006). "Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability". Nature Genetics. 38 (9): 1032–7. doi:10.1038/ng1858. PMID 16906163. S2CID 38047848.
^ Zody MC, Jiang Z, Fung HC, Antonacci F, Hillier LW, Cardone MF, et al. (septembar 2008). "Evolutionary toggling of the MAPT 17q21.31 inversion region". Nature Genetics. 40 (9): 1076–83. doi:10.1038/ng.193. PMC 2684794. PMID 19165922.
^ Almos PZ, Horváth S, Czibula A, Raskó I, Sipos B, Bihari P, et al. (novembar 2008). "H1 tau haplotype-related genomic variation at 17q21.3 as an Asian heritage of the European Gypsy population". Heredity. 101 (5): 416–9. doi:10.1038/hdy.2008.70. PMID 18648385.
^ Hardy J, Pittman A, Myers A, Gwinn-Hardy K, Fung HC, de Silva R, et al. (august 2005). "Evidence suggesting that Homo neanderthalensis contributed the H2 MAPT haplotype to Homo sapiens". Biochemical Society Transactions. 33 (Pt 4): 582–5. doi:10.1042/BST0330582. PMID 16042549.
^ "UniProt, P10636". Pristupljeno 23. 6. 2021.
^ Billingsley ML, Kincaid RL (maj 1997). "Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration". The Biochemical Journal. 323 ( Pt 3) (3): 577–91. doi:10.1042/bj3230577. PMC 1218358. PMID 9169588.
^ Taniguchi T, Kawamata T, Mukai H, Hasegawa H, Isagawa T, Yasuda M, et al. (mart 2001). "Phosphorylation of tau is regulated by PKN". The Journal of Biological Chemistry. 276 (13): 10025–31. doi:10.1074/jbc.M007427200. PMID 11104762.
^ Kanemaru K, Takio K, Miura R, Titani K, Ihara Y (maj 1992). "Fetal-type phosphorylation of the tau in paired helical filaments". Journal of Neurochemistry. 58 (5): 1667–75. doi:10.1111/j.1471-4159.1992.tb10039.x. PMID 1560225. S2CID 94265621.
^ Mawal-Dewan M, Henley J, Van de Voorde A, Trojanowski JQ, Lee VM (decembar 1994). "The phosphorylation state of tau in the developing rat brain is regulated by phosphoprotein phosphatases". The Journal of Biological Chemistry. 269 (49): 30981–7. doi:10.1016/S0021-9258(18)47378-4. PMID 7983034.
^ Matsuo ES, Shin RW, Billingsley ML, Van deVoorde A, O'Connor M, Trojanowski JQ, Lee VM (oktobar 1994). "Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau". Neuron. 13 (4): 989–1002. doi:10.1016/0896-6273(94)90264-X. PMID 7946342. S2CID 40592137.
^ Liu, Fei; Iqbal, Khalid; Grundke-Iqbal, Inge; Hart, Gerald W.; Gong, Cheng-Xin (20. 7. 2004). "O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer's disease". Proceedings of the National Academy of Sciences of the United States of America. 101 (29): 10804–10809. Bibcode:2004PNAS..10110804L. doi:10.1073/pnas.0400348101. ISSN 0027-8424. PMC 490015. PMID 15249677.
^ Alonso AD, Grundke-Iqbal I, Barra HS, Iqbal K (januar 1997). "Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau". Proceedings of the National Academy of Sciences of the United States of America. 94 (1): 298–303. Bibcode:1997PNAS...94..298A. doi:10.1073/pnas.94.1.298. PMC 19321. PMID 8990203.
^ Frost B, Jacks RL, Diamond MI (maj 2009). "Propagation of tau misfolding from the outside to the inside of a cell". The Journal of Biological Chemistry. 284 (19): 12845–52. doi:10.1074/jbc.M808759200. PMC 2676015. PMID 19282288.
^ Calafate S, Buist A, Miskiewicz K, Vijayan V, Daneels G, de Strooper B, et al. (maj 2015). "Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation" (PDF). Cell Reports. 11 (8): 1176–83. doi:10.1016/j.celrep.2015.04.043. PMID 25981034. Arhivirano s originala (PDF), 22. 9. 2017. Pristupljeno 23. 6. 2021.
^ Roman AY, Devred F, Byrne D, La Rocca R, Ninkina NN, Peyrot V, Tsvetkov PO (februar 2019). "Zinc Induces Temperature-Dependent Reversible Self-Assembly of Tau". Journal of Molecular Biology. 431 (4): 687–695. doi:10.1016/j.jmb.2018.12.008. PMID 30580037.
^ Fichou Y, Al-Hilaly YK, Devred F, Smet-Nocca C, Tsvetkov PO, Verelst J, et al. (mart 2019). "The elusive tau molecular structures: can we translate the recent breakthroughs into new targets for intervention?". Acta Neuropathologica Communications. 7 (1): 31. doi:10.1186/s40478-019-0682-x. PMC 6397507. PMID 30823892.
^ Goedert M, Eisenberg DS, Crowther RA (juli 2017). "Propagation of Tau Aggregates and Neurodegeneration". Annual Review of Neuroscience. 40 (1): 189–210. doi:10.1146/annurev-neuro-072116-031153. PMID 28772101.
^ Yamada K (2017). "Extracellular Tau and Its Potential Role in the Propagation of Tau Pathology". Frontiers in Neuroscience (jezik: engleski). 11: 667. doi:10.3389/fnins.2017.00667. PMC 5712583. PMID 29238289.
^ Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T, et al. (novembar 2015). "Depletion of microglia and inhibition of exosome synthesis halt tau propagation". Nature Neuroscience. 18 (11): 1584–93. doi:10.1038/nn.4132. PMC 4694577. PMID 26436904.
^ Nishimura I, Yang Y, Lu B (mart 2004). "PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila". Cell. 116 (5): 671–82. doi:10.1016/S0092-8674(04)00170-9. PMID 15006350. S2CID 18896805.
^ Chatterjee S, Sang TK, Lawless GM, Jackson GR (januar 2009). "Dissociation of tau toxicity and phosphorylation: role of GSK-3beta, MARK and Cdk5 in a Drosophila model". Human Molecular Genetics. 18 (1): 164–77. doi:10.1093/hmg/ddn326. PMC 2644648. PMID 18930955.
^ Lee HG, Perry G, Moreira PI, Garrett MR, Liu Q, Zhu X, et al. (april 2005). "Tau phosphorylation in Alzheimer's disease: pathogen or protector?". Trends in Molecular Medicine. 11 (4): 164–9. doi:10.1016/j.molmed.2005.02.008. hdl:10316/4769. PMID 15823754.
^ Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K (juni 2001). "Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments". Proceedings of the National Academy of Sciences of the United States of America. 98 (12): 6923–8. Bibcode:2001PNAS...98.6923A. doi:10.1073/pnas.121119298. PMC 34454. PMID 11381127.
^ “Alzheimer's Brain Tangles.” Alzheimer's Association, www.alz.org/braintour/tangles.asp.
^ Köglsberger S, Cordero-Maldonado ML, Antony P, Forster JI, Garcia P, Buttini M, et al. (decembar 2017). "Gender-Specific Expression of Ubiquitin-Specific Peptidase 9 Modulates Tau Expression and Phosphorylation: Possible Implications for Tauopathies". Molecular Neurobiology. 54 (10): 7979–7993. doi:10.1007/s12035-016-0299-z. PMC 5684262. PMID 27878758.
^ Hall GF, Patuto BA (juli 2012). "Is tau ready for admission to the prion club?". Prion. 6 (3): 223–33. doi:10.4161/pri.19912. PMC 3399531. PMID 22561167.
^ Jensen PH, Hager H, Nielsen MS, Hojrup P, Gliemann J, Jakes R (septembar 1999). "alpha-synuclein binds to Tau and stimulates the protein kinase A-catalyzed tau phosphorylation of serine residues 262 and 356". The Journal of Biological Chemistry. 274 (36): 25481–9. doi:10.1074/jbc.274.36.25481. PMID 10464279.
^ Giasson BI, Lee VM, Trojanowski JQ (2003). "Interactions of amyloidogenic proteins". Neuromolecular Medicine. 4 (1–2): 49–58. doi:10.1385/NMM:4:1-2:49. PMID 14528052. S2CID 9086733.
^ Klein C, Kramer EM, Cardine AM, Schraven B, Brandt R, Trotter J (februar 2002). "Process outgrowth of oligodendrocytes is promoted by interaction of fyn kinase with the cytoskeletal protein tau". The Journal of Neuroscience. 22 (3): 698–707. doi:10.1523/JNEUROSCI.22-03-00698.2002. PMC 6758498. PMID 11826099.
^ Yu WH, Fraser PE (april 2001). "S100beta interaction with tau is promoted by zinc and inhibited by hyperphosphorylation in Alzheimer's disease". The Journal of Neuroscience. 21 (7): 2240–6. doi:10.1523/JNEUROSCI.21-07-02240.2001. PMC 6762409. PMID 11264299.
^ Baudier J, Cole RD (april 1988). "Interactions between the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase II". The Journal of Biological Chemistry. 263 (12): 5876–83. doi:10.1016/S0021-9258(18)60647-7. PMID 2833519.
^ Hashiguchi M, Sobue K, Paudel HK (august 2000). "14-3-3zeta is an effector of tau protein phosphorylation". The Journal of Biological Chemistry. 275 (33): 25247–54. doi:10.1074/jbc.M003738200. PMID 10840038.

Dopunska literatura

Goedert M, Crowther RA, Garner CC (maj 1991). "Molecular characterization of microtubule-associated proteins tau and MAP2". Trends in Neurosciences. 14 (5): 193–9. doi:10.1016/0166-2236(91)90105-4. PMID 1713721. S2CID 44928661.
Morishima-Kawashima M, Hasegawa M, Takio K, Suzuki M, Yoshida H, Watanabe A, et al. (1995). "Hyperphosphorylation of tau in PHF". Neurobiology of Aging. 16 (3): 365–71, discussion 371–80. doi:10.1016/0197-4580(95)00027-C. PMID 7566346. S2CID 22471158.
Heutink P (april 2000). "Untangling tau-related dementia". Human Molecular Genetics. 9 (6): 979–86. doi:10.1093/hmg/9.6.979. PMID 10767321.
Goedert M, Spillantini MG (juli 2000). "Tau mutations in frontotemporal dementia FTDP-17 and their relevance for Alzheimer's disease". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1502 (1): 110–21. doi:10.1016/S0925-4439(00)00037-5. PMID 10899436.
Morishima-Kawashima M, Ihara Y (novembar 2001). "[Recent advances in Alzheimer's disease]". Seikagaku. The Journal of Japanese Biochemical Society. 73 (11): 1297–307. PMID 11831025.
Blennow K, Vanmechelen E, Hampel H (2002). "CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer's disease". Molecular Neurobiology. 24 (1–3): 87–97. doi:10.1385/MN:24:1-3:087. PMID 11831556. S2CID 24891421.
Ingram EM, Spillantini MG (decembar 2002). "Tau gene mutations: dissecting the pathogenesis of FTDP-17". Trends in Molecular Medicine. 8 (12): 555–62. doi:10.1016/S1471-4914(02)02440-1. PMID 12470988.
Pickering-Brown S (2004). "The tau gene locus and frontotemporal dementia". Dementia and Geriatric Cognitive Disorders. 17 (4): 258–60. doi:10.1159/000077149. PMID 15178931. S2CID 27693523.
van Swieten JC, Rosso SM, van Herpen E, Kamphorst W, Ravid R, Heutink P (2004). "Phenotypic variation in frontotemporal dementia and parkinsonism linked to chromosome 17". Dementia and Geriatric Cognitive Disorders. 17 (4): 261–4. doi:10.1159/000077150. PMID 15178932. S2CID 36197015.
Kowalska A, Jamrozik Z, Kwieciński H (2004). "Progressive supranuclear palsy--parkinsonian disorder with tau pathology". Folia Neuropathologica. 42 (2): 119–23. PMID 15266787.
Rademakers R, Cruts M, van Broeckhoven C (oktobar 2004). "The role of tau (MAPT) in frontotemporal dementia and related tauopathies". Human Mutation. 24 (4): 277–95. doi:10.1002/humu.20086. PMID 15365985. S2CID 28578030.
Lee HG, Perry G, Moreira PI, Garrett MR, Liu Q, Zhu X, et al. (april 2005). "Tau phosphorylation in Alzheimer's disease: pathogen or protector?". Trends in Molecular Medicine. 11 (4): 164–9. doi:10.1016/j.molmed.2005.02.008. hdl:10316/4769. PMID 15823754.
Hardy J, Pittman A, Myers A, Gwinn-Hardy K, Fung HC, de Silva R, et al. (august 2005). "Evidence suggesting that Homo neanderthalensis contributed the H2 MAPT haplotype to Homo sapiens". Biochemical Society Transactions. 33 (Pt 4): 582–5. doi:10.1042/BST0330582. PMID 16042549.
Deutsch SI, Rosse RB, Lakshman RM (decembar 2006). "Dysregulation of tau phosphorylation is a hypothesized point of convergence in the pathogenesis of alzheimer's disease, frontotemporal dementia and schizophrenia with therapeutic implications". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 30 (8): 1369–80. doi:10.1016/j.pnpbp.2006.04.007. PMID 16793187. S2CID 6848053.
Williams DR (oktobar 2006). "Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau". Internal Medicine Journal. 36 (10): 652–60. doi:10.1111/j.1445-5994.2006.01153.x. PMID 16958643. S2CID 19357113.
Pittman AM, Fung HC, de Silva R (oktobar 2006). "Untangling the tau gene association with neurodegenerative disorders". Human Molecular Genetics. 15. 15 Spec No 2 (Review Issue 2): R188-95. doi:10.1093/hmg/ddl190. PMID 16987883.
Roder HM, Hutton ML (april 2007). "Microtubule-associated protein tau as a therapeutic target in neurodegenerative disease". Expert Opinion on Therapeutic Targets. 11 (4): 435–42. doi:10.1517/14728222.11.4.435. PMID 17373874. S2CID 36430988.
van Swieten J, Spillantini MG (januar 2007). "Hereditary frontotemporal dementia caused by Tau gene mutations". Brain Pathology. 17 (1): 63–73. doi:10.1111/j.1750-3639.2007.00052.x. PMID 17493040. S2CID 40879765.
Caffrey TM, Wade-Martins R (juli 2007). "Functional MAPT haplotypes: bridging the gap between genotype and neuropathology". Neurobiology of Disease. 27 (1): 1–10. doi:10.1016/j.nbd.2007.04.006. PMC 2801069. PMID 17555970.
Delacourte A (2005). "Tauopathies: recent insights into old diseases". Folia Neuropathologica. 43 (4): 244–57. PMID 16416389.
Hirokawa N, Shiomura Y, Okabe S (oktobar 1988). "Tau proteins: the molecular structure and mode of binding on microtubules". The Journal of Cell Biology. 107 (4): 1449–59. doi:10.1083/jcb.107.4.1449. PMC 2115262. PMID 3139677.

Vanjski linkovi

Commons logo

Commons ima datoteke na temu: MAPT

tau Proteins na US National Library of Medicine Medical Subject Headings (MeSH)
GeneReviews/NCBI/NIH/UW entry on MAPT-Related Disorders
MR scans of variant CJD CSF tau-positive man
P10636

[refGRCh38Ensembl-1] ENSG00000276155, ENSG00000277956 GRCh38: Ensembl release 89: ENSG00000186868, ENSG00000276155, ENSG00000277956 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000018411 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid3131773-5] Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A (juni 1988). "Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau". Proceedings of the National Academy of Sciences of the United States of America. 85 (11): 4051–5. Bibcode:1988PNAS...85.4051G. doi:10.1073/pnas.85.11.4051. PMC 280359. PMID 3131773.

[pmid2484340-6] Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA (oktobar 1989). "Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease". Neuron. 3 (4): 519–26. doi:10.1016/0896-6273(89)90210-9. PMID 2484340. S2CID 19627629.

[pmid1903170-7] Shin RW, Iwaki T, Kitamoto T, Tateishi J (maj 1991). "Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues". Laboratory Investigation; A Journal of Technical Methods and Pathology. 64 (5): 693–702. PMID 1903170.

[pmid20678581-8] Lei P, Ayton S, Finkelstein DI, Adlard PA, Masters CL, Bush AI (novembar 2010). "Tau protein: relevance to Parkinson's disease". The International Journal of Biochemistry & Cell Biology. 42 (11): 1775–8. doi:10.1016/j.biocel.2010.07.016. PMID 20678581.

[pmid1057175-9] Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW (maj 1975). "A protein factor essential for microtubule assembly". Proceedings of the National Academy of Sciences of the United States of America. 72 (5): 1858–62. Bibcode:1975PNAS...72.1858W. doi:10.1073/pnas.72.5.1858. PMC 432646. PMID 1057175.

[Cleveland_1977-10] Cleveland DW, Hwo SY, Kirschner MW (oktobar 1977). "Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin". Journal of Molecular Biology. 116 (2): 207–25. doi:10.1016/0022-2836(77)90213-3. PMID 599557.

[11] Cleveland DW, Hwo SY, Kirschner MW (oktobar 1977). "Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly". Journal of Molecular Biology. 116 (2): 227–47. doi:10.1016/0022-2836(77)90214-5. PMID 146092.

[pmid31488613-12] ^ ^a ^b ^c ^d ^e ^f Papanikolopoulou K, Roussou IG, Gouzi JY, Samiotaki M, Panayotou G, Turin L, Skoulakis EM (oktobar 2019). "Drosophila Tau Negatively Regulates Translation and Olfactory Long-Term Memory, But Facilitates Footshock Habituation and Cytoskeletal Homeostasis". The Journal of Neuroscience. 39 (42): 8315–8329. doi:10.1523/JNEUROSCI.0391-19.2019. PMC 6794924. PMID 31488613.

[:1-13] Harada A, Oguchi K, Okabe S, Kuno J, Terada S, Ohshima T, et al. (juni 1994). "Altered microtubule organization in small-calibre axons of mice lacking tau protein". Nature. 369 (6480): 488–91. Bibcode:1994Natur.369..488H. doi:10.1038/369488a0. PMID 8202139. S2CID 4322543.

[pmid8202139-14] Wang JZ, Liu F (juni 2008). "Microtubule-associated protein tau in development, degeneration and protection of neurons". Progress in Neurobiology. 85 (2): 148–75. doi:10.1016/j.pneurobio.2008.03.002. PMID 18448228. S2CID 32708424.

[15] Ke YD, Suchowerska AK, van der Hoven J, De Silva DM, Wu CW, van Eersel J, et al. (juni 2012). "Lessons from tau-deficient mice". International Journal of Alzheimer's Disease. 2012 (873270): 873270. doi:10.1155/2012/873270. PMC 3375147. PMID 22720190.

[16] Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, et al. (august 2010). "Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models". Cell. 142 (3): 387–97. doi:10.1016/j.cell.2010.06.036. PMID 20655099. S2CID 18776289.

[17] Dehmelt L, Halpain S (2004). "The MAP2/Tau family of microtubule-associated proteins". Genome Biology. 6 (1): 204. doi:10.1186/gb-2004-6-1-204. PMC 549057. PMID 15642108.

[:2-18] Meier S, Bell M, Lyons DN, Rodriguez-Rivera J, Ingram A, Fontaine SN, et al. (januar 2016). "Pathological Tau Promotes Neuronal Damage by Impairing Ribosomal Function and Decreasing Protein Synthesis". The Journal of Neuroscience. 36 (3): 1001–7. doi:10.1523/JNEUROSCI.3029-15.2016. PMC 4719006. PMID 26791227.

[19] Koren SA, Hamm MJ, Meier SE, Weiss BE, Nation GK, Chishti EA, et al. (april 2019). "Tau drives translational selectivity by interacting with ribosomal proteins". Acta Neuropathologica. 137 (4): 571–583. doi:10.1007/s00401-019-01970-9. PMC 6426815. PMID 30759285.

[20] Dawson HN, Ferreira A, Eyster MV, Ghoshal N, Binder LI, Vitek MP (mart 2001). "Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice". Journal of Cell Science. 114 (Pt 6): 1179–87. doi:10.1242/jcs.114.6.1179. PMID 11228161.

[21] Fujio K, Sato M, Uemura T, Sato T, Sato-Harada R, Harada A (juli 2007). "14-3-3 proteins and protein phosphatases are not reduced in tau-deficient mice". NeuroReport. 18 (10): 1049–52. doi:10.1097/WNR.0b013e32818b2a0b. PMID 17558294. S2CID 25235996.

[:3-22] Ikegami S, Harada A, Hirokawa N (februar 2000). "Muscle weakness, hyperactivity, and impairment in fear conditioning in tau-deficient mice". Neuroscience Letters. 279 (3): 129–32. doi:10.1016/s0304-3940(99)00964-7. PMID 10688046. S2CID 31204860.

[23] Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, et al. (maj 2007). "Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model". Science. 316 (5825): 750–4. Bibcode:2007Sci...316..750R. doi:10.1126/science.1141736. PMID 17478722. S2CID 32771613.

[24] Dawson HN, Cantillana V, Jansen M, Wang H, Vitek MP, Wilcock DM, et al. (august 2010). "Loss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease". Neuroscience. 169 (1): 516–31. doi:10.1016/j.neuroscience.2010.04.037. PMC 2900546. PMID 20434528.

[25] Cantero JL, Hita-Yañez E, Moreno-Lopez B, Portillo F, Rubio A, Avila J (august 2010). "Tau protein role in sleep-wake cycle". Journal of Alzheimer's Disease. 21 (2): 411–21. doi:10.3233/JAD-2010-100285. PMID 20555133.

[26] Sotiropoulos I, Galas MC, Silva JM, Skoulakis E, Wegmann S, Maina MB, et al. (novembar 2017). "Atypical, non-standard functions of the microtubule associated Tau protein". Acta Neuropathologica Communications. 5 (1): 91. doi:10.1186/s40478-017-0489-6. PMC 5707803. PMID 29187252.

[27] Neve RL, Harris P, Kosik KS, Kurnit DM, Donlon TA (decembar 1986). "Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2". Brain Research. 387 (3): 271–80. doi:10.1016/0169-328x(86)90033-1. PMID 3103857.

[28] Sergeant N, Delacourte A, Buée L (januar 2005). "Tau protein as a differential biomarker of tauopathies". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1739 (2–3): 179–97. doi:10.1016/j.bbadis.2004.06.020. PMID 15615637.

[pmid16906163-29] Shaw-Smith C, Pittman AM, Willatt L, Martin H, Rickman L, Gribble S, et al. (septembar 2006). "Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability". Nature Genetics. 38 (9): 1032–7. doi:10.1038/ng1858. PMID 16906163. S2CID 38047848.

[pmid19165922-30] Zody MC, Jiang Z, Fung HC, Antonacci F, Hillier LW, Cardone MF, et al. (septembar 2008). "Evolutionary toggling of the MAPT 17q21.31 inversion region". Nature Genetics. 40 (9): 1076–83. doi:10.1038/ng.193. PMC 2684794. PMID 19165922.

[pmid18648385-31] Almos PZ, Horváth S, Czibula A, Raskó I, Sipos B, Bihari P, et al. (novembar 2008). "H1 tau haplotype-related genomic variation at 17q21.3 as an Asian heritage of the European Gypsy population". Heredity. 101 (5): 416–9. doi:10.1038/hdy.2008.70. PMID 18648385.

[pmid16042549-32] Hardy J, Pittman A, Myers A, Gwinn-Hardy K, Fung HC, de Silva R, et al. (august 2005). "Evidence suggesting that Homo neanderthalensis contributed the H2 MAPT haplotype to Homo sapiens". Biochemical Society Transactions. 33 (Pt 4): 582–5. doi:10.1042/BST0330582. PMID 16042549.

[UniProt-33] "UniProt, P10636". Pristupljeno 23. 6. 2021.

[pmid9169588-34] Billingsley ML, Kincaid RL (maj 1997). "Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration". The Biochemical Journal. 323 ( Pt 3) (3): 577–91. doi:10.1042/bj3230577. PMC 1218358. PMID 9169588.

[pmid11104762-35] Taniguchi T, Kawamata T, Mukai H, Hasegawa H, Isagawa T, Yasuda M, et al. (mart 2001). "Phosphorylation of tau is regulated by PKN". The Journal of Biological Chemistry. 276 (13): 10025–31. doi:10.1074/jbc.M007427200. PMID 11104762.

[pmid1560225-36] Kanemaru K, Takio K, Miura R, Titani K, Ihara Y (maj 1992). "Fetal-type phosphorylation of the tau in paired helical filaments". Journal of Neurochemistry. 58 (5): 1667–75. doi:10.1111/j.1471-4159.1992.tb10039.x. PMID 1560225. S2CID 94265621.

[pmid7983034-37] Mawal-Dewan M, Henley J, Van de Voorde A, Trojanowski JQ, Lee VM (decembar 1994). "The phosphorylation state of tau in the developing rat brain is regulated by phosphoprotein phosphatases". The Journal of Biological Chemistry. 269 (49): 30981–7. doi:10.1016/S0021-9258(18)47378-4. PMID 7983034.

[pmid7946342-38] Matsuo ES, Shin RW, Billingsley ML, Van deVoorde A, O'Connor M, Trojanowski JQ, Lee VM (oktobar 1994). "Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau". Neuron. 13 (4): 989–1002. doi:10.1016/0896-6273(94)90264-X. PMID 7946342. S2CID 40592137.

[39] Liu, Fei; Iqbal, Khalid; Grundke-Iqbal, Inge; Hart, Gerald W.; Gong, Cheng-Xin (20. 7. 2004). "O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer's disease". Proceedings of the National Academy of Sciences of the United States of America. 101 (29): 10804–10809. Bibcode:2004PNAS..10110804L. doi:10.1073/pnas.0400348101. ISSN 0027-8424. PMC 490015. PMID 15249677.

[40] Alonso AD, Grundke-Iqbal I, Barra HS, Iqbal K (januar 1997). "Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau". Proceedings of the National Academy of Sciences of the United States of America. 94 (1): 298–303. Bibcode:1997PNAS...94..298A. doi:10.1073/pnas.94.1.298. PMC 19321. PMID 8990203.

[41] Frost B, Jacks RL, Diamond MI (maj 2009). "Propagation of tau misfolding from the outside to the inside of a cell". The Journal of Biological Chemistry. 284 (19): 12845–52. doi:10.1074/jbc.M808759200. PMC 2676015. PMID 19282288.

[42] Calafate S, Buist A, Miskiewicz K, Vijayan V, Daneels G, de Strooper B, et al. (maj 2015). "Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation" (PDF). Cell Reports. 11 (8): 1176–83. doi:10.1016/j.celrep.2015.04.043. PMID 25981034. Arhivirano s originala (PDF), 22. 9. 2017. Pristupljeno 23. 6. 2021.

[43] Roman AY, Devred F, Byrne D, La Rocca R, Ninkina NN, Peyrot V, Tsvetkov PO (februar 2019). "Zinc Induces Temperature-Dependent Reversible Self-Assembly of Tau". Journal of Molecular Biology. 431 (4): 687–695. doi:10.1016/j.jmb.2018.12.008. PMID 30580037.

[44] Fichou Y, Al-Hilaly YK, Devred F, Smet-Nocca C, Tsvetkov PO, Verelst J, et al. (mart 2019). "The elusive tau molecular structures: can we translate the recent breakthroughs into new targets for intervention?". Acta Neuropathologica Communications. 7 (1): 31. doi:10.1186/s40478-019-0682-x. PMC 6397507. PMID 30823892.

[45] Goedert M, Eisenberg DS, Crowther RA (juli 2017). "Propagation of Tau Aggregates and Neurodegeneration". Annual Review of Neuroscience. 40 (1): 189–210. doi:10.1146/annurev-neuro-072116-031153. PMID 28772101.

[46] Yamada K (2017). "Extracellular Tau and Its Potential Role in the Propagation of Tau Pathology". Frontiers in Neuroscience (jezik: engleski). 11: 667. doi:10.3389/fnins.2017.00667. PMC 5712583. PMID 29238289.

[47] Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T, et al. (novembar 2015). "Depletion of microglia and inhibition of exosome synthesis halt tau propagation". Nature Neuroscience. 18 (11): 1584–93. doi:10.1038/nn.4132. PMC 4694577. PMID 26436904.

[48] Nishimura I, Yang Y, Lu B (mart 2004). "PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila". Cell. 116 (5): 671–82. doi:10.1016/S0092-8674(04)00170-9. PMID 15006350. S2CID 18896805.

[49] Chatterjee S, Sang TK, Lawless GM, Jackson GR (januar 2009). "Dissociation of tau toxicity and phosphorylation: role of GSK-3beta, MARK and Cdk5 in a Drosophila model". Human Molecular Genetics. 18 (1): 164–77. doi:10.1093/hmg/ddn326. PMC 2644648. PMID 18930955.

[50] Lee HG, Perry G, Moreira PI, Garrett MR, Liu Q, Zhu X, et al. (april 2005). "Tau phosphorylation in Alzheimer's disease: pathogen or protector?". Trends in Molecular Medicine. 11 (4): 164–9. doi:10.1016/j.molmed.2005.02.008. hdl:10316/4769. PMID 15823754.

[pmid11381127-51] Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K (juni 2001). "Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments". Proceedings of the National Academy of Sciences of the United States of America. 98 (12): 6923–8. Bibcode:2001PNAS...98.6923A. doi:10.1073/pnas.121119298. PMC 34454. PMID 11381127.

[:0-52] “Alzheimer's Brain Tangles.” Alzheimer's Association, www.alz.org/braintour/tangles.asp.

[pmid_27878758-53] Köglsberger S, Cordero-Maldonado ML, Antony P, Forster JI, Garcia P, Buttini M, et al. (decembar 2017). "Gender-Specific Expression of Ubiquitin-Specific Peptidase 9 Modulates Tau Expression and Phosphorylation: Possible Implications for Tauopathies". Molecular Neurobiology. 54 (10): 7979–7993. doi:10.1007/s12035-016-0299-z. PMC 5684262. PMID 27878758.

[pmid22561167-54] Hall GF, Patuto BA (juli 2012). "Is tau ready for admission to the prion club?". Prion. 6 (3): 223–33. doi:10.4161/pri.19912. PMC 3399531. PMID 22561167.

[pmid10464279-55] Jensen PH, Hager H, Nielsen MS, Hojrup P, Gliemann J, Jakes R (septembar 1999). "alpha-synuclein binds to Tau and stimulates the protein kinase A-catalyzed tau phosphorylation of serine residues 262 and 356". The Journal of Biological Chemistry. 274 (36): 25481–9. doi:10.1074/jbc.274.36.25481. PMID 10464279.

[pmid14528052-56] Giasson BI, Lee VM, Trojanowski JQ (2003). "Interactions of amyloidogenic proteins". Neuromolecular Medicine. 4 (1–2): 49–58. doi:10.1385/NMM:4:1-2:49. PMID 14528052. S2CID 9086733.

[pmid11826099-57] Klein C, Kramer EM, Cardine AM, Schraven B, Brandt R, Trotter J (februar 2002). "Process outgrowth of oligodendrocytes is promoted by interaction of fyn kinase with the cytoskeletal protein tau". The Journal of Neuroscience. 22 (3): 698–707. doi:10.1523/JNEUROSCI.22-03-00698.2002. PMC 6758498. PMID 11826099.

[pmid11264299-58] Yu WH, Fraser PE (april 2001). "S100beta interaction with tau is promoted by zinc and inhibited by hyperphosphorylation in Alzheimer's disease". The Journal of Neuroscience. 21 (7): 2240–6. doi:10.1523/JNEUROSCI.21-07-02240.2001. PMC 6762409. PMID 11264299.

[pmid2833519-59] Baudier J, Cole RD (april 1988). "Interactions between the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase II". The Journal of Biological Chemistry. 263 (12): 5876–83. doi:10.1016/S0021-9258(18)60647-7. PMID 2833519.

[pmid10840038-60] Hashiguchi M, Sobue K, Paudel HK (august 2000). "14-3-3zeta is an effector of tau protein phosphorylation". The Journal of Biological Chemistry. 275 (33): 25247–54. doi:10.1074/jbc.M003738200. PMID 10840038.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

[44]

[45]

[46]

[47]

[48]

[49]

[50]

[51]

[52]

[53]

[54]

[55]

[56]

[57]

[58]

[59]

[60]