Protein homeostasis of a metastable subproteome associated with Alzheimer's disease

Rishika Kundra, Prajwal Ciryam, Richard I. Morimoto, Christopher M. Dobson, Michele Vendruscolo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Alzheimer's disease is the most common cause of dementia. A hallmark of this disease is the presence of aberrant deposits containing by the Aβ peptide (amyloid plaques) and the tau protein (neurofibrillary tangles) in the brains of affected individuals. Increasing evidence suggests that the formation of these deposits is closely associated with the age-related dysregulation of a large set of highly expressed and aggregation-prone proteins, which make up a metastable subproteome. To understand in more detail the origins of such dysregulation, we identify specific components of the protein homeostasis system associated with these metastable proteins by using a gene coexpression analysis. Our results reveal the particular importance of the protein trafficking and clearance mechanisms, including specific branches of the endosomal-lysosomal and ubiquitin-proteasome systems, in maintaining the homeostasis of the metastable subproteome associated with Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)E5703-E5711
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number28
DOIs
StatePublished - Jul 11 2017

Keywords

  • Alzheimer's disease
  • Protein aggregation
  • Protein homeostasis
  • Supersaturation

ASJC Scopus subject areas

  • General

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