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
Related Journals
Related Books
New Findings from Natural Substances
Pharmaceutical Chemistry and Production: An Introductory Textbook
Evidence-Based Research in Ayurveda against COVID-19 in Compliance with Standardized Protocols and Practices
Pharmaceuticals for Targeting Coronaviruses
Medical Applications of Beta-Glucan
Nanotechnology Driven Herbal Medicine for Burns: From Concept to Application
Postbiotics: Science, Technology and Applications
Biologically Active Natural Products from Asia and Africa: A Selection of Topics
83
10
1