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Neurochemical Research

, Volume 44, Issue 1, pp 147–153 | Cite as

Glutamate Dehydrogenase as a Neuroprotective Target Against Neurodegeneration

  • A Young Kim
  • Eun Joo BaikEmail author
Original Paper

Abstract

Regulation of glutamate metabolism via glutamate dehydrogenase (GDH) might be the promising therapeutic approach for treating neurodegenerative disorders. In the central nervous system, glutamate functions both as a major excitatory neurotransmitter and as a key intermediate metabolite for neurons. GDH converts glutamate to α-ketoglutarate, which serves as a TCA cycle intermediate. Dysregulated GDH activity in the central nervous system is highly correlated with neurological disorders. Indeed, studies conducted with mutant mice and allosteric drugs have shown that deficient or overexpressed GDH activity in the brain can regulate whole body energy metabolism and affect early onset of Parkinson’s disease, Alzheimer’s disease, temporal lobe epilepsy, and spinocerebellar atrophy. Moreover, in strokes with excitotoxicity as the main pathophysiology, mice that overexpressed GDH exhibited smaller ischemic lesion than mice with normal GDH expression. In additions, GDH activators improve lesions in vivo by increasing α-ketoglutarate levels. In neurons exposed to an insult in vitro, enhanced GDH activity increases ATP levels. Thus, in an energy crisis, neuronal mitochondrial activity is improved and excitotoxic risk is reduced. Consequently, modulating GDH activity in energy-depleted conditions could be a sound strategy for maintaining the mitochondrial factory in neurons, and thus, protect against metabolic failure.

Keywords

Glutamate dehydrogenase Energy metabolism Neuroprotection Neurodegenerative disorders 

Notes

Acknowledgements

This study was supported by the Korean Research Foundation grant from the Korean government (2012R1A2A01011417), and the Chronic Inflammatory Disease Research Center (NRF-2012R1A5A2048183).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Department of PhysiologyAjou University School of MedicineSuwonSouth Korea
  2. 2.Chronic Inflammatory Disease Research CenterAjou University School of MedicineSuwonSouth Korea

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