Metabotropic glutamate receptor involvement in the pathophysiology of amyotrophic lateral sclerosis: new potential drug targets for therapeutic applications.

Abstract

Amyotrophic lateral sclerosis (ALS) is a complex genetic, late age-onset, progressive neurodegenerative disorder leading to the death of upper and lower motor neurons. Life expectancy after diagnosis is short due to the ongoing degeneration and to the lack of effective treatments. Axonal alterations, mitochondrial deficits, RNA changes, protein misfolding and turnover, glial dysfunction and hyperexcitability are key players in molecular mechanisms involved in the degeneration of motor neurons. In the context of hyperexcitability, metabotropic glutamate (mGlu) receptors, which are widely distributed throughout the central nervous system and act through many intracellular signaling pathways, are emerging as novel potential drug targets for the therapeutic treatment of ALS, as they are able to counteract excitotoxicity by reducing glutamate release and inducing the production of neurotrophic factors.

• Authors: Giuseppe Battaglia, Valeria Bruno
• Journal: Current opinion in pharmacology (Curr Opin Pharmacol) Vol. 38 Pg. 65-71 (02 2018) ISSN: 1471-4973 [Electronic] England
• PMID: 29529498 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Metabotropic Glutamate

Topics

• Amyotrophic Lateral Sclerosis (drug therapy, metabolism)
• Animals
• Humans
• Receptors, Metabotropic Glutamate (metabolism)