Autophagy is an intracellular lysosomal degradation process, which plays an important role in cell growth and development, and keeping cellular homeostasis in all eukaryotes. Autophagy has multiple physiological functions, including protein degradation, organelle turnover and response to stress. Emerging evidences support the notion that dysregulation of autophagy might be critical for pathogenesis of amyotrophic lateral sclerosis (ALS). The autophagy dysregulation in motor neurons of ALS may occur in different steps of the autophagic process. Recent studies have shown that two ALS associated proteins, TDP-43 and superoxide dismutase 1 (SOD1), are involved in the abnormal autophagy regulation. Furthermore, it is reported that several genetic mutations in ALS disturb the autophagic process in the motor neurons. This review will provide new evidence of autophagy dysregulation as a critical pathogenic process leading to ALS, and will discuss the prospect of future therapeutic targets using autophagic regulation to treat this disease.
© 2011 The Authors; Brain Pathology © 2011 International Society of Neuropathology.