Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with few therapeutic options. While several gene mutations have been implicated in ALS, the exact cause of neuronal dysfunction is unknown and motor neurons of affected individuals display numerous cellular abnormalities. Ongoing efforts to develop novel ALS treatments involve the identification of small molecules targeting specific mechanisms of neuronal pathology, including glutamate excitotoxicity, mutant protein aggregation, endoplasmic reticulum (ER) stress, loss of trophic factors, oxidative stress, or neuroinflammation. Herein, we review recent advances in the discovery and preclinical characterization of lead compounds that may ultimately provide novel drugs to treat patients suffering from ALS.

Keywords

• amyotrophic lateral sclerosis (ALS)
• copper/zinc (Cu-Zn) superoxide dismutase 1 (SOD1)
• glutamate toxicity
• neurodegeneration
• oxidative stress