Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1832, Issue 12, Pages 1913-1921Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2013.06.012
Keywords
Mitochondria; Amyloid beta; Amyloid beta precursor protein; Glycogen synthase kinase 3beta; Alzheimer's disease; Voltage-dependent anion channel 1
Funding
- NIH [AG028072, AG042178, RR000163]
- Medical Research Foundation of Oregon
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Glycogen synthase kinase 3 (GSK3) is a serine/threonine protein kinase that is involved in the multiple signaling processes of a cell. Increasing evidence suggests that GSK3 beta plays a key role in multiple cellular processes in the progression of diabetes, obesity, Alzheimer's disease (AD), Parkinson's disease (PD), inflammatory diseases, schizophrenia, bipolar and several mood disorders, and mitochondrial disease's. Recent research has found that increased GSK3 beta activity is linked to the pathogenesis of AD through amyloid beta (A beta) phosphorylated tau and mitochondrial dysfunction. Recent research has also revealed that GSK3 beta is elevated in AD-affected tissues and is critically involved in dissociating the voltage-dependent anion channel 1 (VDAC1) protein from hexokinases, and causing disrupted glucose metabolism, mitochondrial dysfunction and activating apoptotic cell death. The purpose of this article is to review recent research that is elucidating the role of GSK3 beta in AD pathogenesis. We discuss the involvement of GSK3 beta in the phosphorylation of VDAC1 and dissociation of VADC1 with hexokinases in AD neurons. (C) 2013 Elsevier B.V. All rights reserved.
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