Endosomal-Lysosomal Processing of Neurodegeneration-Associated Proteins in Astrocytes

Research output: Contribution to journalReview articlepeer-review

Abstract

Most common neurodegenerative diseases (NDs) are characterized by deposition of protein aggregates that are resulted from misfolding, dysregulated trafficking, and compromised proteolytic degradation. These proteins exert cellular toxicity to a broad range of brain cells and are found in both neurons and glia. Extracellular monomeric and oligomeric ND-associated proteins are taken up by astrocytes, the most abundant glial cell in the brain. Internalization, intracellular trafficking, processing, and disposal of these proteins are executed by the endosomal-lysosomal system of astrocytes. Endosomal-lysosomal organelles thus mediate the cellular impact and metabolic fate of these toxic protein species. Given the indispensable role of astrocytes in brain metabolic homeostasis, the endosomal-lysosomal processing of these proteins plays a fundamental role in altering the trajectory of neurodegeneration. This review aims at summarizing the mounting evidence that has established the essential role of astrocytic endosomal-lysosomal organelles in the processing of amyloid precursor proteins, Apolipoprotein E (ApoE), tau, alpha synuclein, and huntingtin, which are associated with NDs such as Alzheimer’s, Parkinson’s, and Huntington diseases.

Original languageEnglish (US)
Article number5149
Pages (from-to)1-17
Number of pages17
JournalInternational journal of molecular sciences
Volume21
Issue number14
DOIs
StatePublished - Jul 2020

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Keywords

  • APP
  • Alpha synuclein
  • Amyloid beta
  • ApoE
  • Astrocytes
  • Endosome
  • Huntingtin
  • Lysosome
  • Neurodegenerative diseases
  • Tau

Fingerprint

Dive into the research topics of 'Endosomal-Lysosomal Processing of Neurodegeneration-Associated Proteins in Astrocytes'. Together they form a unique fingerprint.

Cite this