THE ROLE OF AUTOPHAGY IN THE PROGRESSION OF AMYOTROPHIC LATERAL SCLEROSIS (ALS): POTENTIAL TARGETS FOR THERAPEUTIC INTERVENTION AND DISEASE MODULATION

Abstract

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder characterized by the degeneration of motor neurons in a progressive manner. Disturbance in cellular homeostasis, especially by disturbed protein degradation, is vital to the pathogenesis of ALS. Autophagy is an important intracellular degradation mechanism to remove protein aggregates and damaged organelles from neurons. Autophagy dysfunction in ALS has been associated with genetic mutations, mitochondrial dysfunction, and proteostasis failure. We explore the mechanistic importance of autophagy in ALS progression, suggest autophagy-targeting therapeutic approaches, and envisage the future research directions to augment the efficacy of treatment in this review.