Autophagy gone awry in neurodegenerative diseases.
Autophagy is essential for neuronal homeostasis, and its dysfunction has been directly linked to a growing number of neurodegenerative disorders. The reasons behind autophagic failure in degenerating neurons can be very diverse because of the different steps required for autophagy and the characterization of the molecular players involved in each of them. Understanding the step(s) affected in the autophagic process in each disorder could explain differences in the course of these pathologies and will be essential to developing targeted therapeutic approaches for each disease based on modulation of autophagy. Here we present examples of different types of autophagic dysfunction described in common neurodegenerative disorders and discuss the prospect of exploring some of the recently identified autophagic variants and the interactions among autophagic and non-autophagic proteolytic systems as possible future therapeutic targets.
Wong
Esther
E
Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York, USA.
Cuervo
Ana Maria
AM
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*