Specific proteins accumulate in neurodegenerative disease, and human genetics has indicated a causative role for many. In most cases, however, the mechanisms remain poorly understood. Degeneration is thought to involve a gain of abnormal function, although we do not know the normal function of many proteins implicated. The protein α-synuclein accumulates in the Lewy pathology of Parkinson's disease and related disorders, and mutations in α-synuclein cause degeneration, but we have not known its normal function or how it triggers disease. α-Synuclein localizes to presynaptic boutons and interacts with membranes in vitro. Overexpression slows synaptic vesicle exocytosis, and recent data suggest a normal role for the endogenous synucleins in dilation of the exocytic fusion pore. Disrupted membranes also appear surprisingly prominent in Lewy pathology. Synuclein thus interacts with membranes under both physiological and pathological conditions, suggesting that the normal function of synuclein may illuminate its role in degeneration.

中文翻译：

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突触核蛋白的膜相互作用：生理学和病理学。

特定蛋白质在神经退行性疾病中积累，人类遗传学已表明许多原因。但是，在大多数情况下，对这些机制的了解仍然很少。变性被认为涉及异常功能的获得，尽管我们不知道所牵涉的许多蛋白质的正常功能。蛋白α-突触核蛋白在帕金森氏病和相关疾病的路易病理学中蓄积，并且α-突触核蛋白的突变会导致变性，但我们尚不知道其正常功能或如何触发疾病。α-突触核蛋白定位于突触前的按钮，并在体外与膜相互作用。过表达减慢了突触小泡的胞吐作用，最近的数据表明内源突触核蛋白在胞外融合孔的扩张中具有正常作用。破裂的膜在路易氏病理学中也出乎意料地突出。因此，突触核蛋白在生理和病理条件下均与膜相互作用，表明突触核蛋白的正常功能可能阐明了其在变性中的作用。