Targeting Aggrephagy for the Treatment of Alzheimer's Disease

Cells. 2020 Jan 28;9(2):311. doi: 10.3390/cells9020311.

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in older individuals with specific neuropsychiatric symptoms. It is a proteinopathy, pathologically characterized by the presence of misfolded protein (Aβ and Tau) aggregates in the brain, causing progressive dementia. Increasing studies have provided evidence that the defect in protein-degrading systems, especially the autophagy-lysosome pathway (ALP), plays an important role in the pathogenesis of AD. Recent studies have demonstrated that AD-associated protein aggregates can be selectively recognized by some receptors and then be degraded by ALP, a process termed aggrephagy. In this study, we reviewed the role of aggrephagy in AD development and discussed the strategy of promoting aggrephagy using small molecules for the treatment of AD.

Keywords: Alzheimer’s disease; aggregates; aggrephagy; selective autophagy.

Publication types

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

MeSH terms

  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / therapy*
  • Animals
  • Humans
  • Lysosomes / metabolism
  • Macroautophagy*
  • Molecular Targeted Therapy
  • Protein Folding
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • TOR Serine-Threonine Kinases