Propagation of Protein Aggregation in Neurodegenerative Diseases

Annu Rev Biochem. 2019 Jun 20;88:785-810. doi: 10.1146/annurev-biochem-061516-045049. Epub 2019 Mar 27.

Abstract

Most common neurodegenerative diseases feature deposition of protein amyloids and degeneration of brain networks. Amyloids are ordered protein assemblies that can act as templates for their own replication through monomer addition. Evidence suggests that this characteristic may underlie the progression of pathology in neurodegenerative diseases. Many different amyloid proteins, including Aβ, tau, and α-synuclein, exhibit properties similar to those of infectious prion protein in experimental systems: discrete and self-replicating amyloid structures, transcellular propagation of aggregation, and transmissible neuropathology. This review discusses the contribution of prion phenomena and transcellular propagation to the progression of pathology in common neurodegenerative diseases such as Alzheimer's and Parkinson's. It reviews fundamental events such as cell entry, amplification, and transcellular movement. It also discusses amyloid strains, which produce distinct patterns of neuropathology and spread through the nervous system. These concepts may impact the development of new diagnostic and therapeutic strategies.

Keywords: aggregation; amyloid; prion; propagation; strain; tau.

Publication types

  • Review

MeSH terms

  • Amyloid
  • Animals
  • Humans
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Protein Aggregation, Pathological*
  • tau Proteins

Substances

  • Amyloid
  • tau Proteins