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α‐Synuclein induces migration of BV‐2 microglial cells by up‐regulation of CD44 and MT1‐MMP
Author(s) -
Kim Seonghan,
Cho SeoHyun,
Kim Ka Young,
Shin Ki Young,
Kim HyeSun,
Park CheolHyoung,
Chang KeunA,
Lee Sang Hyung,
Cho Daeho,
Suh YooHun
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06075.x
Subject(s) - microglia , pars compacta , substantia nigra , microbiology and biotechnology , neurodegeneration , biology , neuroinflammation , cd44 , extracellular matrix , neuroscience , immunology , cell , dopaminergic , inflammation , pathology , biochemistry , medicine , dopamine , disease
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.