Dual Role of Autophagy in Neurodegenerative Diseases: The Case of Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult onset and fatal neurodegenerative disease. A major histophatological hallmark of the disease patient-derived tissue and ALS mouse models is the presence of protein aggregates containing misfolded specific proteins. Strategies to clear out these abnormal protein species are proposed as a possible target for disease intervention. Autophagy, a catabolic route that selective degradates abnormally-folded proteins by the lysosomal pathway, has emerged as an attractive target to treat neurodegenerative diseases, like ALS. Accumulating evidence indicates that autophagy impairment also occurs in ALS and can contribute to the neurodegenerative condition. In this article we discuss the evidence involving autophagy alteration associated to ALS phenotype and the evidence that place autophagy as a therapeutic opportunity to treat this neurodegenerative disease.