The Relation Between α-synuclein and Microglia in Parkinson's Disease: Recent Developments

Neuroscience. 2015 Aug 27;302:47-58. doi: 10.1016/j.neuroscience.2015.02.008. Epub 2015 Feb 12.

Abstract

Recent research suggests a complex role for microglia not only in Parkinson's disease but in other disorders involving alpha-synuclein aggregation, such as multiple system atrophy. In these neurodegenerative processes, the activation of microglia is a common pathological finding, which disturbs the homeostasis of the neuronal environment otherwise maintained, among others, by microglia. The term activation comprises any deviation from what otherwise is considered normal microglia status, including cellular abundance, morphology or protein expression. The microglial response during disease will sustain survival or otherwise promote cell degeneration. The novel concepts of alpha-synuclein being released and uptaken by neighboring cells, and their importance in disease progression, positions microglia as the main cell that can clear and handle alpha-synuclein efficiently. Microglia's behavior will therefore be a determinant on the disease's progression. For this reason we believe that the better understanding of microglia's response to alpha-synuclein pathological accumulation across brain areas and disease stages is essential to develop novel therapeutic tools for Parkinson's disease and other alpha-synucleinopathies. In this review we will revise the most recent findings and developments with regard to alpha-synuclein and microglia in Parkinson's disease.

Keywords: Parkinson’s disease; TLR; alpha-synuclein; microglia; neuroinflammation.

Publication types

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

MeSH terms

  • Animals
  • Brain / pathology*
  • Gene Expression Regulation
  • Humans
  • Interleukin-1beta / metabolism
  • Microglia / metabolism*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • Tumor Necrosis Factor-alpha / metabolism
  • alpha-Synuclein / metabolism*

Substances

  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • alpha-Synuclein