Autophagy in motor neuron disease: Key pathogenetic mechanisms and therapeutic targets

Mol Cell Neurosci. 2016 Apr:72:84-90. doi: 10.1016/j.mcn.2016.01.012. Epub 2016 Feb 2.

Abstract

Autophagy is a lysosome-dependant intracellular degradation process that eliminates long-lived proteins as well as damaged organelles from the cytoplasm. An increasing body of evidence suggests that dysregulation of this system plays a pivotal role in the etiology and/or progression of neurodegenerative diseases including motor neuron disorders. Herein, we review the latest findings that highlight the involvement of autophagy in the pathogenesis of amyotrophic lateral sclerosis (ALS) and the potential role of this pathway as a target of therapeutic purposes. Autophagy promotes the removal of toxic, cytoplasmic aggregate-prone pathogenetic proteins, enhances cell survival, and modulates inflammation. The existence of several drugs targeting this pathway can facilitate the translation of basic research to clinical trials for ALS and other motor neuron diseases.

Keywords: Amyotrophic lateral sclerosis; Authophagy; Protein aggregation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy*
  • Drug Discovery
  • Humans
  • Molecular Targeted Therapy*
  • Motor Neuron Disease / drug therapy
  • Motor Neuron Disease / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases