The Membrane Interactions of Synuclein: Physiology and Pathology.
The Membrane Interactions of Synuclein: Physiology and Pathology.
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突触核蛋白的膜相互作用：生理和病理。
DOI：
10.1146/annurev-pathol-031920-092547
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Gautam Runwal;R. Edwards
中科院分区：
文献类型：
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作者：
Gautam Runwal;R. Edwards
特定的蛋白质在神经退行性疾病中积累，人类遗传学已经表明许多蛋白质的致病作用。然而，在大多数情况下，对这些机制仍然知之甚少。变性被认为涉及异常功能的获得，尽管我们不知道许多涉及的蛋白质的正常功能。蛋白质α-突触核蛋白在帕金森病和相关疾病的路易病理学中积累，α-突触核蛋白的突变导致变性，但我们不知道它的正常功能或如何引发疾病。α-突触核蛋白在体外定位于突触前终扣并与细胞膜相互作用。过表达减缓突触囊泡胞吐，最近的数据表明，在扩张的胞吐融合孔的内源性突触核蛋白的正常作用。破坏的膜在路易氏病理学中也令人惊讶地突出。因此，突触核蛋白在生理和病理条件下与膜相互作用，表明突触核蛋白的正常功能可能阐明其在变性中的作用。
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.