TY - JOUR
T1 - Amyloid beta-induced glycogen synthase kinase 3β phosphorylated VDAC1 in Alzheimer's disease
T2 - Implications for synaptic dysfunction and neuronal damage
AU - Reddy, P. Hemachandra
N1 - Funding Information:
This research was supported by NIH grants AG028072 , AG042178 , and RR000163 , and a grant from the Medical Research Foundation of Oregon .
PY - 2013
Y1 - 2013
N2 - 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 GSK3β 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 diseases. Recent research has found that increased GSK3β activity is linked to the pathogenesis of AD through amyloid beta (Aβ), phosphorylated tau and mitochondrial dysfunction. Recent research has also revealed that GSK3β 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 GSK3β in AD pathogenesis. We discuss the involvement of GSK3β in the phosphorylation of VDAC1 and dissociation of VADC1 with hexokinases in AD neurons.
AB - 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 GSK3β 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 diseases. Recent research has found that increased GSK3β activity is linked to the pathogenesis of AD through amyloid beta (Aβ), phosphorylated tau and mitochondrial dysfunction. Recent research has also revealed that GSK3β 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 GSK3β in AD pathogenesis. We discuss the involvement of GSK3β in the phosphorylation of VDAC1 and dissociation of VADC1 with hexokinases in AD neurons.
KW - Alzheimer's disease
KW - Amyloid beta
KW - Amyloid beta precursor protein
KW - Glycogen synthase kinase 3beta
KW - Mitochondria
KW - Voltage-dependent anion channel 1
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U2 - 10.1016/j.bbadis.2013.06.012
DO - 10.1016/j.bbadis.2013.06.012
M3 - Review article
C2 - 23816568
AN - SCOPUS:84882738357
SN - 0925-4439
VL - 1832
SP - 1913
EP - 1921
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 12
ER -