Modeling Lewy pathology propagation in Parkinson's disease.
Modeling Lewy pathology propagation in Parkinson's disease.
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DOI：
10.1016/s1353-8020(13)70022-1
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发表时间：
2014-01
影响因子：
4.1
通讯作者：
Lee, Virginia M-Y
中科院分区：
文献类型：
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作者：
Luk, Kelvin C;Lee, Virginia M-Y
由α -突触核蛋白（αSyn）组成的路易小体（LBs）和路易神经突（LNs）是帕金森病的神经元内包涵体。虽然路易氏病的病理程度和临床症状之间的联系已经得到了很好的证实，但这些蛋白沉积是如何产生并选择性地靶向易感细胞群的尚不清楚。我们对它们在帕金森病发病机制中的作用的了解也很有限。在这里，我们总结了最近的研究结果，表明这种病理可以通过αSyn的错误折叠形式在动物之间实验传播，αSyn能够通过类似于朊病毒的自繁殖机制启动和诱导LB和LN包涵体的形成。动物模型中的“种子”LBs和LNs也以可预测的模式扩散到多个连接的细胞核，再现了在人类PD进展过程中观察到的现象，导致受影响神经元的功能障碍和变性。这些模型提供了关于这种和其他错误折叠蛋白如何导致人类疾病的神经退行性变的新视角。
Lewy bodies (LBs) and Lewy neurites (LNs) comprised of alpha-synuclein (αSyn), 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 αSyn 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.