Glia and alpha-synuclein in neurodegeneration: A complex interaction

Neurobiol Dis. 2016 Jan;85:262-274. doi: 10.1016/j.nbd.2015.03.003. Epub 2015 Mar 10.

Abstract

α-Synucleinopathies (ASP) comprise adult-onset, progressive neurodegenerative disorders such as Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) that are characterized by α-synuclein (AS) aggregates in neurons or glia. PD and DLB feature neuronal AS-positive inclusions termed Lewy bodies (LB) whereas glial cytoplasmic inclusions (GCIs, Papp-Lantos bodies) are recognized as the defining hallmark of MSA. Furthermore, AS-positive cytoplasmic aggregates may also be seen in astroglial cells of PD/DLB and MSA brains. The glial AS-inclusions appear to trigger reduced trophic support resulting in neuronal loss. Moreover, microgliosis and astrogliosis can be found throughout the neurodegenerative brain and both are key players in the initiation and progression of ASP. In this review, we will highlight AS-dependent alterations of glial function and their impact on neuronal vulnerability thereby providing a detailed summary on the multifaceted role of glia in ASP.

Keywords: Astroglia; Dementia with Lewy bodies; Glial cytoplasmic inclusions; Lewy bodies; Microglia; Multiple system atrophy; Oligodendroglia; Parkinson's disease; α-Synuclein.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Nerve Degeneration / metabolism
  • Neurodegenerative Diseases / metabolism*
  • Neuroglia / metabolism*
  • alpha-Synuclein / metabolism*

Substances

  • alpha-Synuclein