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P3–305: C–terminal Src kinase (CSK) is diminished in lipid rafts in Alzheimer's disease
Author(s) -
Puig Berta,
Santpere Gabriel,
Ferrer Isidre
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1575
Subject(s) - lipid raft , kinase , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , sh3 domain , tyrosine kinase , sphingolipid , chemistry , biology , signal transduction
Background: Lipid rafts or cholesterol-sphingolipid enriched domains are small membrane microdomains proposed as important platforms for cellular signalling where proteins can be included or excluded depending on the presence of hydrophobic modifications or adaptor proteins. In Alzheimer s Disease (AD), lipid rafts have become an intense subject of study because their composition is altered and related to the developement of the disease. AD is neuropathologically characterised by the presence of -amyloid plaques and aggregates of hyperphosphorylated tau. Objective: We have focused our studies in the Src-family kinases, an important group of non-receptor tyrosine-kinases (SFKs), present in lipid rafts and able to activate GSK-3, a kinase with the capacity to hyperphosphorylate tau in vivo. Methods: We have performed immunohistochemistry, lipid raft isolation and western blot analysis from brains with AD and age-matched controls. Conclusions: We have found that CSK, the main inhibitor kinase of several members of the Src-family kinases, is present in neurofibrillary tangles (NFTs) and that, although total levels are not decreased, its presence in lipid rafts is diminished. Therefore, a deregulation of the activity of the Src-family kinases can contribute to the neuropathology in AD.