Spreading of alpha-synuclein - relevant or epiphenomenon?

J Neurochem. 2019 Sep;150(5):605-611. doi: 10.1111/jnc.14779. Epub 2019 Jul 9.

Abstract

The intracellular accumulation of misfolded alpha-synuclein pathology, termed Lewy pathology, throughout the brain is a phenomenon central to Parkinson's disease pathogenesis. In recent years it has become apparent that Lewy pathology can spread from neuron-to-neuron and between interconnected brain regions. Understanding the phenomenon of Lewy pathology propagation holds great promise in its explanatory power to determine the etiology of Parkinson's disease and related synucleinopathies. However, it remains to be seen if the spread of Lewy pathology is critical for driving this disease. Here we discuss the spreading of Lewy pathology while highlighting some important concepts and experimental observations. We conclude that further studies are required to determine if, and how, the spreading behavior of Lewy pathology is involved in Parkinson's disease. "This article is part of the Special Issue Synuclein".

Keywords: Braak hypothesis; neurodegeneration; prion; synucleinopathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloid / metabolism
  • Animals
  • Biopolymers
  • Brain / pathology*
  • Disease Progression
  • Gene-Environment Interaction
  • Humans
  • Interneurons / metabolism
  • Lewy Bodies / pathology
  • Mice
  • Mice, Transgenic
  • Models, Neurological
  • Neurons / metabolism*
  • Organ Specificity
  • Parkinson Disease / etiology
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Prions / metabolism
  • Protein Aggregates
  • Protein Transport
  • Recombinant Proteins / metabolism
  • alpha-Synuclein / metabolism*

Substances

  • Amyloid
  • Biopolymers
  • Prions
  • Protein Aggregates
  • Recombinant Proteins
  • alpha-Synuclein