Park Ji-Young, Paik Seung R, Jou Ilo, Park Sang Myun
Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea.
Glia. 2008 Aug 15;56(11):1215-23. doi: 10.1002/glia.20691.
Gathering evidence has associated activation of microglia with the pathogenesis of numerous neurodegenerative diseases of the central nervous system (CNS) such as Alzheimer's disease and Parkinson's disease. Microglia are the resident macrophages of the CNS whose functions include chemotaxis, phagocytosis, and secretion of a variety of cytokines and proteases. In this study, we examined the possibility that alpha-synuclein (alpha-syn), which is associated with the pathogenesis of Parkinson's disease, may affect the phagocytic function of microglia. We found that extracellular monomeric alpha-syn enhanced microglial phagocytosis in both a dose- and time-dependent manner, but beta- and gamma- syn did not. We also found that the N-terminal and NAC region of alpha-syn, especially the NAC region, might be responsible for the effect of alpha-syn on microglial phagocytosis. In contrast to monomeric alpha-syn, aggregated alpha-syn actually inhibited microglial phagocytosis. The different effects of monomeric and aggregated alpha-syn on phagocytosis might be related to their localization in cells. This study indicates that alpha-syn can modulate the function of microglia and influence inflammatory changes such as those seen in neurodegenerative disorders.
已有证据表明，小胶质细胞的激活与多种中枢神经系统（CNS）神经退行性疾病（如阿尔茨海默病和帕金森病）的发病机制相关。小胶质细胞是中枢神经系统中的常驻巨噬细胞，其功能包括趋化性、吞噬作用以及分泌多种细胞因子和蛋白酶。在本研究中，我们探讨了与帕金森病发病机制相关的α-突触核蛋白（α-syn）是否可能影响小胶质细胞的吞噬功能。我们发现，细胞外单体α-syn以剂量和时间依赖性方式增强小胶质细胞的吞噬作用，但β-和γ-突触核蛋白则无此作用。我们还发现，α-syn的N端和NAC区域，尤其是NAC区域，可能是α-syn对小胶质细胞吞噬作用产生影响的原因。与单体α-syn不同，聚集的α-syn实际上抑制了小胶质细胞的吞噬作用。单体和聚集的α-syn对吞噬作用的不同影响可能与其在细胞中的定位有关。本研究表明，α-syn可调节小胶质细胞的功能，并影响神经退行性疾病中所见的炎症变化。
