Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia PA, 19104, USA.
Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1(0 1):S85-7. doi: 10.1016/S1353-8020(13)70022-1.
Lewy bodies (LBs) and Lewy neurites (LNs), comprised of alpha-synuclein (aSyn), are intraneuronal inclusions that characterize Parkinson's disease. Although the association between the extent of Lewy pathology and clinical symptoms is well established, how these proteinaceous deposits originate and target selectively vulnerable cell populations is unknown. Our knowledge of their role in PD pathogenesis is also limited. Here, we summarize recent findings demonstrating this pathology can be experimentally transmitted between animals by misfolded forms of aSyn that are capable of initiating and inducing LB and LN inclusion formation through a self-propagating mechanism reminiscent of prions. "Seeded" LBs and LNs in animal models also spread to multiple connected nuclei in a predictable pattern, recapitulating a phenomenon observed during human PD progression, leading to the dysfunction and degeneration of afflicted neurons. These models provide new perspectives on how this and other misfolded proteins may contribute to neurodegeneration in human disease.
路易体（Lewy bodies，LB）和路易神经突（Lewy neurites，LN）由α-突触核蛋白（alpha-synuclein，aSyn）组成，是特征性存在于帕金森病患者神经元内的包涵体。尽管路易病理学的严重程度与临床症状之间存在密切关联，但这些蛋白沉积物的起源以及选择性靶向易损细胞群的机制尚不清楚。我们对其在帕金森病发病机制中的作用的了解也很有限。在这里，我们总结了最近的发现，这些发现表明，通过能够引发和诱导 LB 和 LN 包含物形成的错误折叠形式的 aSyn，路易体病理学可以在动物之间通过实验传播，这一机制类似于朊病毒，通过自我传播的机制启动。在动物模型中，“接种”的 LB 和 LN 也以可预测的模式传播到多个连接的核团，再现了在人类 PD 进展过程中观察到的现象，导致受累神经元的功能障碍和退化。这些模型为理解这种以及其他错误折叠蛋白如何导致人类疾病中的神经退行性变提供了新的视角。
