Intrinsically disordered proteins identified in the aggregate proteome serve as biomarkers of neurodegeneration

Metab Brain Dis. 2022 Jan;37(1):147-152. doi: 10.1007/s11011-021-00791-8. Epub 2021 Aug 4.

Abstract

A protein's structure is determined by its amino acid sequence and post-translational modifications, and provides the basis for its physiological functions. Across all organisms, roughly a third of the proteome comprises proteins that contain highly unstructured or intrinsically disordered regions. Proteins comprising or containing extensive unstructured regions are referred to as intrinsically disordered proteins (IDPs). IDPs are believed to participate in complex physiological processes through refolding of IDP regions, dependent on their binding to a diverse array of potential protein partners. They thus play critical roles in the assembly and function of protein complexes. Recent advances in experimental and computational analyses predicted multiple interacting partners for the disordered regions of proteins, implying critical roles in signal transduction and regulation of biological processes. Numerous disordered proteins are sequestered into aggregates in neurodegenerative diseases such as Alzheimer's disease (AD) where they are enriched even in serum, making them good candidates for serum biomarkers to enable early detection of AD.

Keywords: Aggregate proteome; Biomarker; Intrinsically disordered proteins; Neurodegneration; Protein aggregation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Amino Acid Sequence
  • Biomarkers
  • Humans
  • Intrinsically Disordered Proteins* / chemistry
  • Intrinsically Disordered Proteins* / metabolism
  • Proteome / chemistry
  • Proteome / metabolism

Substances

  • Biomarkers
  • Intrinsically Disordered Proteins
  • Proteome