Corruption and spread of pathogenic proteins in neurodegenerative diseases

J Biol Chem. 2012 Sep 28;287(40):33109-15. doi: 10.1074/jbc.R112.399378. Epub 2012 Aug 9.

Abstract

With advancing age, the brain becomes increasingly susceptible to neurodegenerative diseases, most of which are characterized by the misfolding and errant aggregation of certain proteins. The induction of aggregation involves a crystallization-like seeding mechanism by which a specific protein is structurally corrupted by its misfolded conformer. The latest research indicates that, once formed, proteopathic seeds can spread from one locale to another via cellular uptake, transport, and release. Impeding this process could represent a unified therapeutic strategy for slowing the progression of a wide range of currently intractable disorders.

Publication types

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

MeSH terms

  • Aging
  • Amyloidogenic Proteins / chemistry
  • Animals
  • Brain / metabolism
  • Hippocampus / pathology
  • Humans
  • Huntington Disease / metabolism
  • Lewy Body Disease / metabolism
  • Mice
  • Mice, Transgenic
  • Neurodegenerative Diseases / metabolism*
  • Parkinson Disease / metabolism
  • Prions / chemistry
  • Protein Binding
  • Protein Conformation
  • Protein Folding

Substances

  • Amyloidogenic Proteins
  • Prions