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Aberrant Control of Motoneuronal Excitability in Amyotrophic Lateral Sclerosis: Excitatory Glutamate / D ‐Serine vs. Inhibitory Glycine/ γ ‐Aminobutanoic Acid (GABA)
Author(s) -
Sasabe Jumpei,
Aiso Sadakazu
Publication year - 2010
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200900306
Subject(s) - amyotrophic lateral sclerosis , glutamate receptor , neuroscience , excitotoxicity , inhibitory postsynaptic potential , ionotropic effect , chemistry , nmda receptor , excitatory postsynaptic potential , glycine , riluzole , endogeny , biology , biochemistry , receptor , amino acid , medicine , disease
The mechanism underlying selective motoneuronal loss in amyotrophic lateral sclerosis (ALS) remains uncertain. The pathogenesis appears to be a complex and multifactorial process. Glutamate excitotoxicity to motoneuron is one of the most intensely investigated targets for the treatment of ALS, and excessive motoneuronal excitation by glutamate through ionotropic glutamate receptors has been mainly demonstrated. However, development of clinically effective drug targeting glutamate is sometimes difficult, because some aspects of glutamergic signals also could be beneficial, as the injured neurons attempt to recruit endogenous recovery. This review is focused on identifying other mechanisms of imbalanced excitation in ALS motoneurons including excitation‐modulating D ‐serine and inhibitory glycine/GABA. Further, validation of these mechanisms might ultimately lead us to new therapeutic targets for ALS.