Your search for: 'author:("Santpere, Gabriel")' has returned 2 results. (0.005s) Save search

Authors: Martín, Virginia | Fabelo, Noemí | Santpere, Gabriel | Puig, Berta | Marín, Raquel | Ferrer, Isidre | Díaz, Mario

Article Type: Research Article

Abstract: Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes …(mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24–85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD. Show more

Keywords: Alzheimer's disease, docosahexaenoic acid, human brain cortex, lipid rafts, membrane phospholipids, polyunsaturated fatty acids

DOI: 10.3233/JAD-2010-1242

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 489-502, 2010

Authors: Huesa, Gema | Baltrons, María Antonia | Gómez-Ramos, Pilar | Morán, Asunción | García, Agustina | Hidalgo, Juan | Francés, Silvia | Santpere, Gabriel | Ferrer, Isidre | Galea, Elena

Article Type: Research Article

Abstract: RhoGTPases control cytoskeleton dynamics thereby modulating synaptic plasticity. Because Alzheimer's disease (AD) is characterized by synaptic dysfunction, we sought to determine whether the expression, activity, or localization of the GTPases RhoA, Rac1 and Cdc42, as well as p21-PAK, a downstream target of Rac1/Cdc42, were altered in 18-month-old AβPP Tg2576 mice (Swedish mutation) or in brains from patients with AD and, for comparison in the case of RhoA, Pick's disease (PiD), a neurodegenerative disorder characterized by hyper-phosphorylated tau accumulation. Immunohistochemical analyses revealed a distinct localization of each RhoGTPase in synapses, dendrite shafts, neuronal bodies, or astrocytes. The association of RhoA with …synapses and dendritic microtubules was confirmed by electron microscopy. In AβPP mice, RhoA expression decreased in synapses and increased in dystrophic neurites, suggesting altered subcellular targeting of RhoA. In AD, RhoA immunostaining decreased in the neuropil and markedly increased in neurons, co-localizing with hyperphosphorylated tau inclusions, as though RhoA were sequestered by neurofibrillary tangles. Additionally, total RhoA protein was lower in the AD brain hippocampus, reflecting loss of the membrane bound, presumably active, GTPase. RhoA colocalized with hyperphosphorylated tau in PiD, again suggesting that altered subcellular targeting of RhoA is related to neurodegeneration. No major immunohistochemical changes were observed for Rac1, Cdc42, or p21-PAK, thus identifying RhoA among RhoGTPases as a possible therapeutic target in AD. Show more

Keywords: Actin, cytoskeleton, microtubules, neurofibrillary tangles, Pick's disease, synaptic terminals, tau

DOI: 10.3233/JAD-2010-1203

Citation: Journal of Alzheimer's Disease, vol. 19, no. 1, pp. 37-56, 2010