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Regulation of tau phosphorylation and protection against β‐amyloid‐induced neurodegeneration by lithium. Possible implications for Alzheimer's disease
Author(s) -
Alvarez Gema,
MuñozMontaño Juan Ramón,
Satrústegui Jorgina,
Avila Jesús,
Bogónez Elena,
DíazNido Javier
Publication year - 2002
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1034/j.1399-5618.2002.01150.x
Subject(s) - gsk 3 , neurodegeneration , hyperphosphorylation , glycogen synthase , gsk3b , alzheimer's disease , tau protein , biochemistry of alzheimer's disease , amyloid (mycology) , kinase , amyloid precursor protein , amyloid beta , lithium (medication) , neuroscience , phosphorylation , biology , microbiology and biotechnology , chemistry , biochemistry , peptide , medicine , endocrinology , disease , pathology
Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of the β‐amyloid peptide and the hyperphosphorylation of the tau protein, among other features. The most widely accepted hypothesis on the etiopathogenesis of this disease proposes that the aggregates of the β‐amyloid peptide are the main triggers of tau hyperphosphorylation and the subsequent degeneration of affected neurons. In support of this view, fibrillar aggregates of synthetic β‐amyloid peptide induce tau hyperphosphorylation and cell death in cultured neurons. We have previously reported that lithium inhibits tau hyperphosphorylation and also significantly protects cultured neurons from cell death triggered by β‐amyloid peptide. As lithium is a relatively specific inhibitor of glycogen synthase kinase‐3 (in comparison with other protein kinases), and other studies also point to a relevant role of this enzyme, we favor the view that glycogen synthase kinase‐3 is a crucial element in the pathogenesis of Alzheimer's disease. In our opinion, the possibility of using lithium, or other inhibitors of glycogen synthase kinase‐3, in experimental trials aimed to ameliorate neurodegeneration in Alzheimer's disease should be considered.