Development of novel therapeutic strategies against neurodegenerative diseases targeting on abnormal protein aggregates

α-突触核蛋白(ASYN)是丝状包涵体的主要成分，构成帕金森氏病和路易体痴呆的典型特征。然而，ASYN积累和传播的分子机制尚不清楚。在本研究中，我们发现脑内注射重组ASYN的纤维有效地诱导了野生型小鼠的ASYN病理，而注射可溶性ASYN的小鼠则没有。免疫印迹分析显示，内源性小鼠ASYN在接种后3个月开始积累，而注射的人ASYN纤维在大约一周内消失。这些结果表明ASYN原纤维具有蛋白样属性，接种到野生型脑中可在活体内诱导ASYN病理。这是一种新的散发性非核糖核病小鼠模型，对于阐明进展机制和评估疾病修正疗法应该是有用的。

Alpha-Synuclein (asyn) is the major component of filamentous inclusions that constitute the defining characteristic of Parkinson's disease and dementia with Lewy bodies. However, the molecular mechanisms underlying asyn accumulation and spread are unclear.In this study, we show that intracerebral injections of fibrils of recombinant asyn efficiently induced asyn pathologies in wild-type mice, whereas mice injected with soluble asyn did not. Immunoblot analysis demonstrated that endogenous mouse asyn started to accumulate 3 months after inoculation, while injected human asyn fibrils disappeared in about a week. These results indicate that asyn fibrils have prion-like properties and inoculation into wild-type brain induces asyn pathology in vivo. This is a new mouse model of sporadic asynucleinopathy, and should be useful for elucidating progression mechanisms and evaluating disease-modifying therapy.