α-Synuclein induces migration of BV-2 microglial cells by up-regulation of CD44 and MT1-MMP

Seonghan Kim, Seo Hyun Cho, Ka Young Kim, Ki Young Shin, Hye Sun Kim, Cheol Hyoung Park, Keun A. Chang, Sang Hyung Lee, Daeho Cho, Yoo Hun Suh

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Although there is known to be a marked concentration of reactive microglia in the substantia nigra pars compacta (SNpc) of patients with Parkinson's disease (PD), a disorder in which α-synuclein plays a key pathogenic role, the specific roles of α-synuclein and microglia remains poorly understood. In this study, we investigated the effects of α-synuclein and the mechanisms of invasive microglial migration into the SNpc. We show that α-synuclein up-regulates the expressions of the cell adhesion molecule CD44 and the cell surface protease membrane-type 1 matrix metalloproteinase through the extracellular regulated kinases 1/2 pathway. These concurrent inductions increased the generation of soluble CD44 to liberate microglia from the surrounding extracellular matrix for migration. The effects of α-synuclein were identical in BV-2 murine microglial cells subjected to cDNA transfection and extracellular treatment. These inductions in primary microglial cultures of C57Bl/6 mice were identical to those in BV-2 cells. α-Synuclein-induced microglial migration into the SNpc was confirmed in vivo using a 6-hydroxydopamine mouse model of PD. Our data demonstrate a correlation between α-synuclein-induced phenotypic changes and microglial migration. With the recruitment of the microglial population into the SNpc during dopaminergic neurodegeneration, α-synuclein may play a role in accelerating the pathogenesis of PD.

Original languageEnglish
Pages (from-to)1483-1496
Number of pages14
JournalJournal of Neurochemistry
Volume109
Issue number5
DOIs
Publication statusPublished - 2009 Jun

Keywords

  • CD44
  • Membrane-type 1 matrix metalloproteinase
  • Microglia
  • Migration
  • α-synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'α-Synuclein induces migration of BV-2 microglial cells by up-regulation of CD44 and MT1-MMP'. Together they form a unique fingerprint.

  • Cite this

    Kim, S., Cho, S. H., Kim, K. Y., Shin, K. Y., Kim, H. S., Park, C. H., Chang, K. A., Lee, S. H., Cho, D., & Suh, Y. H. (2009). α-Synuclein induces migration of BV-2 microglial cells by up-regulation of CD44 and MT1-MMP. Journal of Neurochemistry, 109(5), 1483-1496. https://doi.org/10.1111/j.1471-4159.2009.06075.x