title: Aberrant control of motoneuronal excitability in amyotrophic lateral sclerosis: excitatory glutamate/D-serine vs. inhibitory glycine/gamma-aminobutanoic acid (GABA).
abstract: 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.
authors.affiliation: Department of Anatomy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan. sasabe@sc.itc.keio.ac.jp
authors.forename: Jumpei
authors.initials: J
authors.lastname: Sasabe
authors.forename: Sadakazu
authors.initials: S
authors.lastname: Aiso
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000628:therapy; D018846:Excitatory Amino Acids / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018846:Excitatory Amino Acids; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D012694:Serine; D005680:gamma-Aminobutyric Acid; D005998:Glycine