Autophagy stimulation as a promising approach in treatment of neurodegenerative diseases

Metab Brain Dis. 2018 Aug;33(4):989-1008. doi: 10.1007/s11011-018-0214-6. Epub 2018 Mar 14.

Abstract

Autophagy is a process of degradation of macromolecules in the cytoplasm, particularly proteins of a long half-life, as well as whole organelles, in eukaryotic cells. Lysosomes play crucial roles during this degradation. Autophagy is a phylogenetically old, and evolutionarily conserved phenomenon which occurs in all eukaryotic cells. It can be found in yeast Saccharomyces cerevisiae, insect Drosophila melanogaster, and mammals, including humans. Its high importance for cell physiology has been recognized, and in fact, dysfunctions causing impaired autophagy are associated with many severe disorders, including cancer and metabolic brain diseases. The types and molecular mechanisms of autophagy have been reviewed recently by others, and in this paper they will be summarized only briefly. Regulatory networks controlling the autophagy process are usually described as negative regulations. In contrast, here, we focus on different ways by which autophagy can be stimulated. In fact, activation of this process by different factors or processes can be considered as a therapeutic strategy in metabolic neurodegenerative diseases. These aspects are reviewed and discussed in this article.

Keywords: Autophagy stimulation; Lysosomes; Neurodegenerative diseases; Therapeutic strategies.

Publication types

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

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Humans
  • Lysosomes / metabolism
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Signal Transduction / drug effects

Substances

  • Neuroprotective Agents