| First Author | Choi YR | Year | 2015 |
| Journal | Neurobiol Dis | Volume | 83 |
| Pages | 90-9 | PubMed ID | 26342897 |
| Mgi Jnum | J:260637 | Mgi Id | MGI:6142657 |
| Doi | 10.1016/j.nbd.2015.08.025 | Citation | Choi YR, et al. (2015) FcgammaRIIB mediates the inhibitory effect of aggregated alpha-synuclein on microglial phagocytosis. Neurobiol Dis 83:90-9 |
| abstractText | Parkinson''s disease (PD) is the second most prevalent neurodegenerative disease. Although the etiology of PD has not yet been fully understood, accumulating evidence indicates that neuroinflammation plays a critical role in the progression of PD. alpha-Synuclein (alpha-Syn) has been considered to be a key player of the pathogenesis of PD, and recent reports that prion-like propagation of misfolded alpha-syn released from neurons may play an important role in the progression of PD have led to increased attention to the studies elucidating the roles of extracellular alpha-syn in the CNS. Extracellular alpha-syn has also been reported to regulate microglial inflammatory response. In this study, we demonstrated that aggregated alpha-syn inhibited microglial phagocytosis by activating SHP-1. SHP-1 activation was also observed in A53T alpha-syn transgenic mice. In addition, aggregated alpha-syn bound to FcgammaRIIB on microglia, inducing SHP-1 activation, further inhibiting microglial phagocytosis. Aggregated alpha-syn upregulated FcgammaRIIB expression in microglia and upregulated FcgammaRIIB was also observed in A53T alpha-syn transgenic mice. These data suggest that aggregated alpha-syn released from neurons dysregulates microglial immune response through inhibiting microglial phagocytosis, further causing neurodegeneration observed in PD. The interaction of aggregated alpha-syn and FcgammaRIIB and further SHP-1 activation can be a new therapeutic target against PD. |
