Aberrant Control of Motoneuronal Excitability in Amyotrophic Lateral Sclerosis: Excitatory Glutamate / D-Serine vs. Inhibitory Glycine/γ-Aminobutanoic Acid (GABA)
✍ Scribed by Jumpei Sasabe; Sadakazu Aiso
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 218 KB
- Volume
- 7
- Category
- Article
- ISSN
- 1612-1872
No coin nor oath required. For personal study only.
✦ Synopsis
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.