Molecular and cellular mechanism of glutamate receptors in relation to amyotrophic lateral sclerosis.
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.
Iwasaki
Yasuo
Y
Fourth Department of Internal Medicine, Toho University Ohashi Hospital, 2-17-6, Ohashi, Meguro-ku, Tokyo 153-8515, Japan. yaso@med.toho-u.ac.jp
Ikeda
Ken
K
Kinoshita
Masao
M
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D017470:Receptors, Glutamate / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018698:Glutamic Acid