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KEGG    Network variation - Pathways of neurodegeneration
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ENTRYnt06466
NamePathways of neurodegeneration
CategoryDisease view; Neurodegenerative disease
Pathwayhsa05022 Pathways of neurodegeneration - multiple diseases
DiseaseH00056 Alzheimer disease
H00057 Parkinson disease
H00058 Amyotrophic lateral sclerosis
H00059 Huntington disease
H00063 Spinocerebellar ataxia
H00061 Prion disease
Display drug-target relation   disease type
Calcium signaling
N00953      Glutamate→GRM1→GNAQ→PLCB→IP3→ITPR→Ca2+→PKC⊣TRPC3→Ca2+
N00960    SCA   SPTBN2*⊣GRM1→GNAQ→PLCB→IP3→ITPR→Ca2+
N00954    SCA   Glutamate→GRM1*→GNAQ→PLCB→IP3→ITPR→Ca2+
N00958    SCA   Glutamate→GRM1→GNAQ→PLCB→IP3→ITPR1*→Ca2+
N00959    SCA   Glutamate→GRM1→GNAQ→PLCB→IP3→ITPR1*⌿Ca2+
N00955    SCA   Glutamate→GRM1→GNAQ→PLCB→IP3→ITPR→Ca2+→PRKCG*⌿TRPC3
N00956    SCA   Glutamate→GRM1→GNAQ→PLCB→IP3→ITPR→Ca2+→PRKCG*⊣TRPC3
N00961    SCA             TRPC3*→Ca2+
N01032    PD       PRKN*→PLCG1→IP3→ITPR→Ca2+
N00984      Glutamate→GRM5→GNAQ→PLCB→IP3→ITPR→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS=APAF1→CASP9→(CASP3,CASP7)
N01002    AD APP*→Abeta→GRM5→GNAQ→PLCB→IP3→ITPR→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS=APAF1→CASP9→CASP3
N01151    ALS           SIGMAR1*→ITPR→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS
N01008    AD           PSEN1*→ITPR→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS
N01007    AD           (PSEN1*,PSEN2*)→RYR3→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS=APAF1→CASP9→(CASP3,CASP7)
N01199    PrD           PRNP*→(RYR,ITPR)→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS=APAF1→CASP9→CASP3
N00985    HD   Glutamate→GRM5→GNAQ→PLCB→IP3→(ITPR+HTT*)→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS=APAF1→CASP9→(CASP3,CASP7)
N00957    SCA   Glutamate→GRM1→GNAQ→PLCB→IP3→(ITPR1+(ATXN2*,ATX..→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS
N01000      ACh→mAChR→GNAQ→PLCB→IP3→ITPR→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS
N01001    AD APP*→Abeta→mAChR→GNAQ→PLCB→IP3→ITPR→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS
N00967              Ca2+(extracellular..−VGCC→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS=APAF1→CASP9→(CASP3,CASP7)
N00986    HD         HTT*⊣STX1A⊣VGCC(N-type)→Ca2+
N01004    AD         APP*→Abeta→VGCC(L-type)→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS
N01201    PrD           PRNP*⊣VGCC(N,L-type)→Ca2+
N01006    AD               APP*→Abeta→PPID→MPTP→CYCS
N01031    PD           Ca2+(extracellular..−SNCA*→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS=APAF1→CASP9→CASP3
N00968    SCA           Ca2+(extracellular..−CACNA1A*→Ca2+
N00969    SCA           Ca2+(extracellular..⌿CACNA1A*⌿Ca2+
N00970              Glutamate→NMDAR→Ca2+
N00987    HD         HTT*⌿DLG4→NMDAR→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS=APAF1→CASP9→CASP3
N01200    PrD           PRNP*→NMDAR→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS=APAF1→CASP9→CASP3
N00971    SCA           PDYN*→NMDAR→Ca2+
N01003    AD         APP*→Abeta→NMDAR→Ca2+−MCU→Ca2+(mito)−MPTP→CYCS
 
Ubiquitin-proteasome system
N01019    UBCH7/8=PRKN⊣alphaSp22
N01020    PD UBCH7/8⌿PRKN*⌿alphaSp22
N01021    UBCH7/8=PRKN⊣PAELR
N01022    PD UBCH7/8⌿PRKN*⌿PAELR
N01023    UBCH7/8=PRKN⊣CDCREL1
N01024    PD UBCH7/8⌿PRKN*⌿CDCREL1
N01025    UBCH7/8=PRKN⊣SYPH1
N01026    PD UBCH7/8⌿PRKN*⌿SYPH1
N01029        (Protein+UB)−26S→Peptide
N01144    ALS SOD1*⊣DERL1→(Protein+UB)−26S→Peptide
N01145    ALS   VCP*⊣(Protein+UB)−26S→Peptide
N01146    ALS   UBQLN2*⊣(Protein+UB)−26S→Peptide
N01060    AD   APP*→Abeta⊣26S
N01030    PD     SNCA*⊣26S
N01061    HD     HTT*⊣26S
N01197    PrD     PRNP*⊣26S
N01027    UB(chain)−UCHL1→UB(free)
N01028    PD UB(chain)⌿UCHL1*⌿UB(free)
 
Unfolded protein response (UPR) signaling
N01009        EIF2AK3→EIF2S1→ATF4⇒DDIT3
N01010    AD   PSEN1*⊣EIF2AK3→EIF2S1→ATF4⇒DDIT3
N01035    PD SNCA*⊣BIP⊣EIF2AK3→EIF2S1→ATF4⇒DDIT3
N01149    ALS SOD1*⊣BIP⊣EIF2AK3→EIF2S1→ATF4⇒DDIT3
N01198    PrD PRNP*⊣BIP⊣EIF2AK3→EIF2S1→ATF4⇒DDIT3
N01011        ERN1→XBP1⇒DDIT3
N01012    AD   PSEN1*⊣ERN1→XBP1
N01034    PD SNCA*⊣BIP⊣ERN1→XBP1
N01148    ALS SOD1*⊣BIP⊣ERN1→XBP1
N01013    ERN1→TRAF2→MAP3K5→MAP2K7→JNK
N01014    AD APP*→Abeta→MAP3K5→MAP2K7→JNK
N01015        ATF6⇒(DDIT3,XBP1,HSPA5)
N01016    AD   PSEN1*⊣ATF6⇒(DDIT3,XBP1)
N01150    ALS   VAPB*⊣ATF6
N01033    PD SNCA*⊣BIP⊣ATF6⇒DDIT3
N01147    ALS SOD1*⊣BIP⊣ATF6⇒DDIT3
 
Autophagy
N01142    RAB1A→(C9orf72+WDR41+SMC..→ULK1_complex
N01143    ALS RAB1A⌿(C9orf72*+WDR41+SM..⌿(ULK1+RB1CC1+ATG10..
N00155    mTORC1→ULK1_complex→PI3KC3-C1
N00962    SCA   ATXN3*⌿(BECN1+PIK3C3+ATG1..
N00993    HD   HTT*⊣(BECN1+PIK3C3+ATG1..
 
Mitophagy
N01052    PINK1→PRKN⊣MFN1/2
N01053    PD PINK1*⌿PRKN⌿MFN1/2
N01054    PD   PRKN*⌿MFN1/2
N01137    PINK1→PRKN→(CISD1,CISD2,FAF2,..=(SQSTM1,OPTN,NDP52..=LC3
N01138    ALS PINK1→PRKN→(CISD1,CISD2,FAF2,..⌿OPTN*
N01139    ALS PINK1→PRKN→(CISD1,CISD2,FAF2,..⌿SQSTM1*⌿LC3
N01140    TBK1→(SQSTM1,OPTN,NDP52..=LC3-II
N01141    ALS TBK1*⌿(SQSTM1,OPTN,NDP52..=LC3-II
 
Apoptosis
N00146      (FASLG,TNFSF10)→(FAS,TNFRSF10B)→FADD→(CASP8,CASP10)→BID→(BAX,BAK1)→CYCS=APAF1→CASP9→(CASP3,CASP7)
N01005    AD APP*→Abeta→FAS→FADD→CASP8→BID→(BAX,BAK1)→CYCS=APAF1→CASP9→CASP3
N00098            (PMAIP1,BBC3,BAD,B..⊣(BCL2,BCL2L1)⊣(BAX,BAK1)→CYCS=APAF1→CASP9→(CASP3,CASP7)
N01135    ALS         SOD1*⊣BCL2⊣(BAX,BAK1)→CYCS=APAF1→CASP9→CASP3
N01051    PD         DJ1*⌿BCL2L1⌿BAX
N01050    PD         PINK1*⌿PRKN⌿BAX→CYCS=APAF1→CASP9→CASP3
N01049    PD           PRKN*⌿BAX→CYCS=APAF1→CASP9→CASP3
N01048    PD           PINK1*⌿(HTRA2,TRAP1)⌿CYCS=APAF1→CASP9→CASP3
N01047    PD             LRRK2*→CYCS=APAF1→CASP9→CASP3
 
AGE-RAGE signaling
N00994      AGE→AGER→RAS→RAF→MEK→ERK→NFKB⇒(TNF,IL6,NOS2)
N00996    AD APP*→Abeta→AGER→RAS→RAF→MEK→ERK→NFKB⇒(TNF,IL6,NOS2)
 
Oxidative phosphorylation
N00995                  NADH−CxI→Q
N00997    AD APP*→Abeta→CHRNA7→Ca2+→CAPN→CDK5R1=CDK5→MAPT⊣CxI→Q
N01136    ALS               TARDBP*⊣CxI→Q
N01042    PD               SNCA*⊣CxI→Q
N01043    PD               PINK1*⊣CxI→Q
N01044    PD               MPP+⊣CxI→Q
N01045    PD               Rotenone⊣CxI→Q
N00988    Succinate−CxII→QH2
N00989    HD HTT*⊣CxII→QH2
N01402    AD,PD Mn2+⊣CxII→QH2
N00990    QH2−CxIII→CytC
N00991    HD HTT*⊣CxIII→CytC
N01046    PD Maneb⊣CxIII→CytC
N00998      CytC−CxIV→H2O
N00999    AD APP*→Abeta⊣CxIV→H2O
 
Microtubule-based transport
N00976                  (DCTN+DNAH+DNAI+DN..=(TUBA+TUBB)
N00977    HD             (HTT*+HAP1)⊣(DCTN+DNAH+DNAI+DN..=(TUBA+TUBB)
N01160    ALS             SOD1*⊣(DCTN+DNAH+DNAI+DN..
N01158    ALS               DCTN1*⌿(TUBA+TUBB)
N01159    ALS               (DCTN+DNAH+DNAI+DN..⌿TUBA4A*
N00978                  (KIF5+KLC)=(TUBA+TUBB)
N01055    PD             SNCA*⊣(KIF5+KLC)⌿(TUBA+TUBB)
N00979    HD           HTT*→JNK3⊣(KIF5+KLC)=(TUBA+TUBB)
N01017    AD           PSEN1*→GSK3B⊣(KIF5+KLC)
N01202    PrD           PRNP*→(GSK3B,CK2)⊣(KIF5+KLC)
N01018    AD APP*→Abeta→CHRNA7→Ca2+→CAPN→CDK5R1=CDK5→MAPT⊣(TUBA+TUBB)
N01403    AD           Zn2+→GSK3B→MAPT⊣(TUBA+TUBB)
N01414    AD           Fe2+→CDK5→MAPT⊣(TUBA+TUBB)

Disease nameDisease category
SCAH00063Spinocerebellar ataxia (SCA)Neurodegenerative disease
PDH00057Parkinson diseaseNeurodegenerative disease
ADH00056Alzheimer diseaseNeurodegenerative disease
ALSH00058Amyotrophic lateral sclerosis (ALS)Neurodegenerative disease
PrDH00061Prion diseaseNeurodegenerative disease
HDH00059Huntington diseaseNeurodegenerative disease
AD,PDH00056Alzheimer diseaseNeurodegenerative disease
H00057Parkinson diseaseNeurodegenerative disease