CXCL12 is involved in α-synuclein-triggered neuroinflammation of Parkinson's disease

J Neuroinflammation. 2019 Dec 12;16(1):263. doi: 10.1186/s12974-019-1646-6.


Background: The mechanisms underlying the pathogenesis and progression of Parkinson's disease (PD) remain elusive, but recent opinions and perspectives have focused on whether the inflammation process induced by microglia contributes to α-synuclein-mediated toxicity. Migration of microglia to the substantia nigra (SN) could precede neurodegeneration in A53T mice. We hypothesized that CXCL12 could be a mediator in the α-synuclein-induced migration of microglia.

Methods: After establishing appropriate animal and cell culture models, we explored the relationship between α-synuclein and CXCL12 in A53T mice, primary microglia, and BV-2 cell lines. We also explored the mechanisms of these interactions and the signaling processes involved in neuroinflammation.

Results: We confirmed the positive correlation between α-synuclein and CXCL12 in the postmortem brain tissue of PD patients and the upregulated CXCR4 expression in SN microglia of A53T mice. In addition, as expected, α-synuclein increased the production of CXCL12 in microglia via TLR4/IκB-α/NF-κB signaling. Importantly, CXCL12/CXCR4/FAK/Src/Rac1 signaling was shown to be involved in α-synuclein-induced microglial accumulation.

Conclusions: Our study suggests that CXCL12 could be a novel target for the prevention of α-synuclein-triggered ongoing microglial responses. Blocking CXCL12/CXCR4 may be a potential therapeutic approach for PD progression.

Keywords: CXCL12; Microglia; Parkinson’s disease; α-Synuclein.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Line, Transformed
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism*
  • Female
  • Humans
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • RAW 264.7 Cells
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*
  • alpha-Synuclein / toxicity*


  • CXCL12 protein, human
  • Chemokine CXCL12
  • alpha-Synuclein