Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
J Neuroimmunol. 2023 Mar 15;376:578047. doi: 10.1016/j.jneuroim.2023.578047. Epub 2023 Feb 8.
Alpha-synuclein is a neuronal protein with unclear function but is associated with the pathogenesis of Parkinson's disease and other synucleinopathies. In this review, we discuss the emerging functional role of alpha-synuclein in support of the unique immune responses in the nervous system. Recent data now show that alpha-synuclein functions to support interferon signaling within neurons and is released from neurons to support chemoattraction and activation of local glial cells and infiltrating immune cells. Inflammatory activation and interferon signaling also induce post-translational modifications of alpha-synuclein that are commonly associated with Parkinson's disease pathogenesis. Taken together, emerging data implicate complex interactions between alpha-synuclein and host immune responses that may contribute to the pathogenesis of Parkinson's disease. Additional study of the function of alpha-synuclein in the brain's immune response may provide disease-modifying therapeutic targets for Parkinson's disease in the future.
α-突触核蛋白是一种神经元蛋白，其功能尚不清楚，但与帕金森病和其他突触核蛋白病的发病机制有关。在这篇综述中，我们讨论了 α-突触核蛋白在支持神经系统中独特免疫反应方面的新兴功能作用。最近的数据表明，α-突触核蛋白在神经元中支持干扰素信号转导，并从神经元中释放出来，以支持趋化和激活局部神经胶质细胞和浸润免疫细胞。炎症激活和干扰素信号转导也诱导 α-突触核蛋白的翻译后修饰，这些修饰通常与帕金森病的发病机制有关。总之，新出现的数据表明 α-突触核蛋白与宿主免疫反应之间存在复杂的相互作用，这可能有助于帕金森病的发病机制。进一步研究 α-突触核蛋白在大脑免疫反应中的功能，可能为未来帕金森病的治疗提供疾病修饰的治疗靶点。
