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Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Review Article

Role of Hexokinase and VDAC in Neurological Disorders

Author(s): José César Rosa and Marcelo de Cerqueira César

Volume 9 , Issue 4 , 2016

Page: [320 - 331] Pages: 12

DOI: 10.2174/1874467209666160112123036

Price: $65

Abstract

Several neurological diseases such as bipolar disorders and schizophrenia are linked to impaired brain energy metabolism. A key feature of brain bioenergetics is hexokinase (HK) binding to the outer mitochondrial membrane through the voltage dependent anion channel (VDAC). This has metabolic consequences, with phosphorylation of glucose by mitochondrially bound hexokinase being closely coupled to production of substrate ATP by intramitochondrial oxidative phosphorylation. Additionally, binding of HK to mitochondria inhibits Bax-induced cytochrome c release and apoptosis. Moreover VDAC1 expression level is elevated in cerebellum of patients with Down ´s syndrome, while in Alzheimer ´s disease, VDAC1 levels are decreased in frontal cortex and VDAC2 elevated in temporal cortex. Thus, understanding the roles of VDAC and HK, either separate or interacting in brain, provides new opportunities and challenges to elucidate pathophysiological mechanisms for future therapeutic strategies.

Keywords: Energy metabolism, glycolysis, hexokinase, lactate, neurons, VDAC.

Graphical Abstract

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