Departments of Neurology and Physiology, Graduate Programs in Biomedical Sciences, Cell Biology and Neuroscience, UCSF School of Medicine, San Francisco, CA 94158-2517, USA.
Neuron. 2013 Sep 18;79(6):1044-66. doi: 10.1016/j.neuron.2013.09.004.
Human genetics has indicated a causal role for the protein α-synuclein in the pathogenesis of familial Parkinson's disease (PD), and the aggregation of synuclein in essentially all patients with PD suggests a central role for this protein in the sporadic disorder. Indeed, the accumulation of misfolded α-synuclein now defines multiple forms of neural degeneration. Like many of the proteins that accumulate in other neurodegenerative disorders, however, the normal function of synuclein remains poorly understood. In this article, we review the role of synuclein at the nerve terminal and in membrane remodeling. We also consider the prion-like propagation of misfolded synuclein as a mechanism for the spread of degeneration through the neuraxis.
人类遗传学表明，蛋白质α-突触核蛋白在家族性帕金森病（PD）的发病机制中起因果作用，而在几乎所有 PD 患者中突触核蛋白的聚集表明该蛋白在散发性疾病中起核心作用。事实上，错误折叠的α-突触核蛋白的积累现在定义了多种形式的神经退行性变。然而，与在其他神经退行性疾病中积累的许多蛋白质一样，突触核蛋白的正常功能仍知之甚少。在本文中，我们回顾了突触核蛋白在神经末梢和膜重塑中的作用。我们还考虑了错误折叠的突触核蛋白类似朊病毒的传播作为通过神经轴传播退化的机制。
