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Glutamate Dehydrogenase Deficiency in Cerebellar Degenerations: Clinical, Biochemical and Molecular Genetic Aspects

Published online by Cambridge University Press:  18 September 2015

Plaitakis Andreas ,
Flessas Panayiotis ,
B. Natsiou Anastasia  and
P. Shashidharan
Plaitakis Andreas*
Affiliation:
Department of Neurology, Mount Sinai School of Medicine, New York (A.P., P.S.); University of Crete, School of Health Sciences, Iraklion, Crete, Greece (P.F., A.B.N.)
Flessas Panayiotis*
Affiliation:
Department of Neurology, Mount Sinai School of Medicine, New York (A.P., P.S.); University of Crete, School of Health Sciences, Iraklion, Crete, Greece (P.F., A.B.N.)
B. Natsiou Anastasia*
Affiliation:
Department of Neurology, Mount Sinai School of Medicine, New York (A.P., P.S.); University of Crete, School of Health Sciences, Iraklion, Crete, Greece (P.F., A.B.N.)
P. Shashidharan*
Affiliation:
Department of Neurology, Mount Sinai School of Medicine, New York (A.P., P.S.); University of Crete, School of Health Sciences, Iraklion, Crete, Greece (P.F., A.B.N.)
*
Department of Neurology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, N.Y., USA 10029
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Abstract:

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Glutamate dehydrogenase (GDH), an enzyme central to glutamate metabolism, is significantly reduced in patients with heterogenous neurological disorders characterized by multiple system atrophy (MSA) and predominant involvement of the cerebellum and its connections. In human brain, GDH exists in multiple isoforms differing in their isoelectric point and molecular mass. These are differentially reduced in quantity and altered in catalytic activity in patients with clinically distinct forms of MSA, thus suggesting that these GDH isoproteins are under different genetic control. Dysregulation of glutamate metabolism occurs in patients with GDH deficiency and is thought to mediate the disease’s neurodegeneration via neuroexcitotoxic mechanisms. This possibility is supported by additional data showing that glutamate binding sites are significantly decreased in cerebellar tissue obtained at autopsy from MSA patients. At the molecular biological level, several cDNAs specific for human GDH have been isolated recently and cloned. Northern blot analysis of various human tissues, including brain, has revealed the presence of multiple GDH-specific mRNAs. In addition, multiple GDH-specific genes are present in humans and these data are consistent with the possibility that the various GDH isoproteins are encoded by different genes. These advances have laid the groundwork for characterizing the human GDH genes and their products in health and disease.

Type
Abstract
Information
Canadian Journal of Neurological Sciences , Volume 20 , Issue S3 , May 1993 , pp. S109 - S116
Copyright
Copyright © Canadian Neurological Sciences Federation 1993

References

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