Synapsin III is a key component of α-synuclein fibrils in Lewy bodies of PD brains

Brain Pathol. 2018 Nov;28(6):875-888. doi: 10.1111/bpa.12587. Epub 2018 Feb 23.

Abstract

Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of α-synuclein (α-syn), are neuropathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal phosphoprotein synapsin III (syn III) controls dopamine release via cooperation with α-syn and modulates α-syn aggregation. Here, we observed that LB and LN, in the substantia nigra of PD patients and hippocampus of one subject with DLB, displayed a marked immunopositivity for syn III. The in situ proximity ligation assay revealed the accumulation of numerous proteinase K-resistant neuropathological inclusions that contained both α-syn and syn III in tight association in the brain of affected subjects. Most strikingly, syn III was identified as a component of α-syn-positive fibrils in LB-enriched protein extracts from PD brains. Finally, a positive correlation between syn III and α-syn levels was detected in the caudate putamen of PD subjects. Collectively, these findings indicate that syn III is a crucial α-syn interactant and a key component of LB fibrils in the brain of patients affected by PD.

Keywords: Lewy bodies; Lewy body dementia; Parkinson's disease; synapsin III; α-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Dopamine / metabolism
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Lewy Bodies / metabolism*
  • Lewy Bodies / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology*
  • Putamen / metabolism
  • Putamen / pathology
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Synapsins / metabolism*
  • alpha-Synuclein / metabolism*

Substances

  • SYN3 protein, human
  • Synapsins
  • alpha-Synuclein
  • Dopamine