Glutamate dehydrogenase: Potential therapeutic targets for neurodegenerative disease

Abstract

Glutamate dehydrogenase (GDH) is a key enzyme in mammalian glutamate metabolism. It is located at the intersection of multiple metabolic pathways and participates in a variety of cellular activities. GDH activity is strictly regulated by a variety of allosteric compounds. Here, we review the unique distribution and expressions of GDH in the brain nervous system. GDH plays an essential role in the glutamate-glutamine-GABA cycle between astrocytes and neurons. The dysfunction of GDH may induce the occurrence of many neurodegenerative diseases, such as Parkinson's disease, epilepsy, Alzheimer's disease, schizophrenia, and frontotemporal dementia. GDH activators and gene therapy have been found to protect neurons and improve motor disorders in neurodegenerative diseases caused by glutamate metabolism disorders. To date, no medicine has been discovered that specifically targets neurodegenerative diseases, although several potential medicines are used clinically. Targeting GDH to treat neurodegenerative diseases is expected to provide new insights and treatment strategies.

Keywords: Glutamate dehydrogenase; Glutamate-glutamine-GABA cycle; Neurodegenerative diseases; Neuroprotection.