The use of pharmacological retromer chaperones in Alzheimer's disease and other endosomal-related disorders. Review uri icon

Overview

abstract

  • The retromer is an evolutionary conserved multiprotein complex involved in the sorting and retrograde trafficking of cargo from endosomal compartments to the Golgi network and to the cell surface. The neuronal retromer traffics the amyloid precursor protein away from the endosomes, a site where amyloid precursor protein is enzymatically cleaved into pathogenic fragments in Alzheimer's disease. In recent years, deficiencies in retromer-mediated transport have been implicated in several neurological and non-neurological diseases, including Parkinson's disease, suggesting that improving the efficacy of the retromer trafficking pathway would result in decreased pathology. We recently identified a new family of small molecules that appear to stabilize the interaction between members of the retromer complex and enhance its function in neurons: the retromer pharmacological chaperones. Here we discuss the role of these molecules in the improvement of retromer trafficking and endosomal dysfunction, as well as their potential as therapeutics for neurological and non-neurological disorders.

publication date

  • January 1, 2015

Research

keywords

  • Alzheimer Disease
  • Endosomes
  • Multiprotein Complexes
  • Neuroprotective Agents

Identity

PubMed Central ID

  • PMC4322078

Scopus Document Identifier

  • 84939980974

Digital Object Identifier (DOI)

  • 10.1016/j.neurobiolaging.2004.09.018

PubMed ID

  • 25472693

Additional Document Info

volume

  • 12

issue

  • 1