The Role of Glutamate Dehydrogenase Activity in Development of Neurodegenerative Disorders

Abstract

The specific role of Glutamate dehydrogenase (GLDH) in the brain is not yet clear, but it is an important enzyme in protein degradation as well as a metabolism regulator of glutamate as a neurotransmitter. The enzyme probably provides crucial protection for postsynaptic membranes against the neurotoxic effects of glutamate neurotransmitters. In men, GLDH activity declines almost evenly through the ages; in women, it declines faster in the first five decades. In the years of menopause, GLDH activity declines slower. The diminished GLDH activities in leukocytes and in the brain vary considerably, but they are parallel with the progress of neurodegenerative diseases. The GLDH activity is partly deficient in the brain, particularly in the leukocytes of patients with heterogeneous neurological disorders and degeneration of multiple neuronal systems. We found a statistically significant difference of GLDH activity in the cerebrospinal fluid in patients with neurological diseases and unexpected in patients with degenerative and inflammatory disorders. The decrease in GLDH activity in the cerebrospinal fluid of patients with neurodegenerative disorders may be one of the reasons for the neuro-excitotoxic glutamate effect. Defining the GLDH activity in leukocytes is at the moment the sole experimental method. The second one could be the measurement in cerebrospinal fluid. The results suggest a possibility to regulate glutamate level in human brain through activation of GLDH.