Description
GSK3α is a multifunctional protein serine kinase, homologous to Drosophila shaggy (zeste-white3) and implicated in the control of several regulatory proteins including glycogen synthase and transcription factors (e.g., JUN). GSK3α also plays a role in the WNT and PI3K signaling pathways. Alzheimer disease is associated with increased production and aggregation of amyloid-beta-40 and -42 peptides into plaques. GSK3α is required for maximal production of the beta-amyloid-40 and -42 peptides generated from the amyloid precursor protein by presenilin-dependent gamma-secretase cleavage. In vitro, lithium, a GSK3α?inhibitor, blocks the production of the beta-amyloid peptides by interfering with the gamma-secretase step