In the neurodegenerative disease multiple system atrophy (MSA), α-synuclein misfolds into a self-templating conformation to become a prion. To compare the biological activity of α-synuclein prions in MSA and Parkinson’s disease (PD), we developed nine α-synuclein−YFP cell lines expressing point mutations responsible for inherited PD. MSA prions robustly infected wild-type, A30P, and A53T α-synuclein–YFP cells, but they were unable to replicate in cells expressing the E46K mutation. Coexpression of the A53T and E46K mutations was unable to rescue MSA prion infection in vitro, establishing that MSA α-synuclein prions are conformationally distinct from the misfolded α-synuclein in PD patients. This observation may have profound implications for developing treatments for neurodegenerative diseases.

中文翻译：

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家族性帕金森氏症的点突变消除了多系统萎缩病毒的复制

在神经退行性疾病多系统萎缩症（MSA）中，α-突触核蛋白错误折叠成自模板构象，成为become病毒。为了比较α-突触核蛋白蛋白在MSA和帕金森氏病（PD）中的生物学活性，我们开发了9种α-突触核蛋白-YFP细胞系，它们表达引起遗传性PD的点突变。MSA pr病毒可强烈感染野生型，A30P和A53Tα-突触核蛋白-YFP细胞，但它们无法在表达E46K突变的细胞中复制。A53T和E46K突变的共表达无法在体外挽救MSA pr病毒感染，从而确定了PD患者中MSAα-突触核蛋白ions蛋白在构象上与错折叠的α-突触核蛋白不同。这一发现对于开发神经退行性疾病的治疗方法可能具有深远的意义。