Current Drug Target -CNS & Neurological Disorders

Stephen D. Skaper
Department of Pharmaceutical and Pharmacological Sciences
University of Padova
Padova
Italy

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Molecular and Cellular Mechanism of Glutamate Receptors in Relation to Amyotrophic Lateral Sclerosis

Author(s): Yasuo Iwasaki, Ken Ikeda and Masao Kinoshita

Affiliation: Fourth Department of Internal Medicine, Toho University Ohashi Hospital, 2-17-6, Ohashi, Meguro-ku, Tokyo 153-8515, Japan.

Keywords: excitatory amino acids, glutamate, glutamate receptors, excitotoxicity, amyotrophic lateral sclerosis

Abstract:

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of the central nervous system (CNS) with an unknown etiology. This disorder is characterized clinically by muscular weakness and wasting, and pathologically by selective degeneration of the corticospinal tracts and motor neurons of the brain stem and spinal cord. Median survival following onset is 3 to 5 years. Riluzole, an antiglutamatergic agent has been shown to have modest beneficial effects on survival. Glutamate is the main excitatory neurotransmitter in the CNS and excessive activation of glutamate receptors is excitotoxic to neurons. Glutamate receptor-mediated excitotoxicity has been proposed to explain the pattern of selective neuronal cell death and clinical manifestation of ALS. Activation of glutamate receptors leading to elevation of intracellular calcium may play a major role. This review will focus on the current understanding of the molecular and cellular mechanisms of glutamate receptors in relation to ALS.

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Article Details

VOLUME: 1
ISSUE: 5
Page: [511 - 518]
Pages: 8
DOI: 10.2174/1568007023339021