Endosomal-lysosomal dysfunctions in Alzheimer's disease: Pathogenesis and therapeutic interventions

Metab Brain Dis. 2021 Aug;36(6):1087-1100. doi: 10.1007/s11011-021-00737-0. Epub 2021 Apr 21.

Abstract

The endosomal-lysosomal system mediates the process of protein degradation through endocytic pathway. This system consists of early endosomes, late endosomes, recycling endosomes and lysosomes. Each component in the endosomal-lysosomal system plays individual crucial role and they work concordantly to ensure protein degradation can be carried out functionally. Dysregulation in the endosomal-lysosomal system can contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). In AD endosomal-lysosomal abnormalities are the earliest pathological features to note and hence it is important to understand the involvement of endosomal-lysosomal dysfunction in the pathogenesis of AD. In-depth understanding of this dysfunction can allow development of new therapeutic intervention to prevent and treat AD.

Keywords: Alzheimer's disease; Endosomal‐lysosomal system; Endosome trafficking; Lysosomal defects; Neurodegeneration; Pathogenesis; Therapeutic interventions.

Publication types

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

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism*
  • Brain / metabolism
  • Brain / pathology
  • Endosomes / metabolism*
  • Endosomes / pathology
  • Humans
  • Lysosomes / metabolism*
  • Lysosomes / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Proteolysis