Mitochondrial dysfunction and synaptic damage have been described as early events in Alzheimer's disease (AD) pathogenesis. Recent research using AD postmortem brains, and AD mouse and cell models revealed that amyloid beta (A beta) and tau hyperphosphorylation are involved in mitochondrial dysfunction and synaptic damage in AD. Further, recent research also revealed that the protein levels of mitochondrial outer membrane protein, voltage-dependent anion channel 1 (VDAC1), are elevated in the affected regions of AD postmortem brains and cortical tissues from APP transgenic mice. In addition, emerging research using AD postmortem brains and AD mouse models revealed that VDAC1 is linked to A beta and phosphorylated tau, blocks the mitochondrial permeability transition (MPT) pores, disrupts the transport of mitochondrial proteins and metabolites, impairs gating of VDAC, and causes defects in oxidative phosphorylation, leading to mitochondrial dysfunction in AD neurons. The purpose of this article is to review research that has investigated the relationship between VDAC1 and the regulation of MPT pores in AD progression. (C) 2012 Elsevier B.V. All rights reserved.

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.