Aberrant control of motoneuronal excitability in amyotrophic lateral sclerosis: Excitatory glutamate/D-serine vs. inhibitory glycine/γ- aminobutanoic acid (GABA)

Jumpei Sasabe, Sadakazu Aiso

Research output: Contribution to journalReview article

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1479-1490
Number of pages12
JournalChemistry and Biodiversity
Volume7
Issue number6
DOIs
Publication statusPublished - 2010 Jun

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ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Molecular Medicine
  • Molecular Biology

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