Ubiquilin-1 and protein quality control in alzheimer disease

Amina El Ayadi, Emily S. Stieren, José M. Barral, Darren Boehning

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

Single nucleotide polymorphisms in the ubiquilin-1 gene may confer risk for late-onset Alzheimer disease (AD). We have shown previously that ubiquilin-1 functions as a molecular chaperone for the amyloid precursor protein (APP) and that protein levels of ubiquilin-1 are decreased in the brains of AD patients. We have recently found that ubiquilin-1 regulates APP trafficking and subsequent secretase processing by stimulating non-degradative ubiquitination of a single lysine residue in the cytosolic domain of APP. Thus, ubiquilin- 1 plays a central role in regulating APP biosynthesis, trafficking and ultimately toxicity. As ubiquilin-1 and other ubiquilin family members have now been implicated in the pathogenesis of numerous neurodegenerative diseases, these findings provide mechanistic insights into the central role of ubiquilin proteins in maintaining neuronal proteostasis.

Original languageEnglish (US)
Pages (from-to)164-169
Number of pages6
JournalPrion
Volume7
Issue number2
DOIs
StatePublished - Mar 1 2013

Keywords

  • Alzheimer disease
  • Amyloid precursor protein
  • Molecular chaperone
  • Trafficking
  • Ubiquilin-1
  • Ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Infectious Diseases

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