帕金森病中的选择性神经元易损性。
Selective neuronal vulnerability in Parkinson disease.
作者信息
Surmeier D James, Obeso José A, Halliday Glenda M
机构信息
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Centro Integral de Neurociencias A.C. (CINAC), HM Puerta del Sur, Hospitales de Madrid, Mostoles and CEU San Pablo University, 28938 Madrid, Spain.
出版信息
Nat Rev Neurosci. 2017 Jan 20;18(2):101-113. doi: 10.1038/nrn.2016.178.
Abstract
Intracellular α-synuclein (α-syn)-rich protein aggregates called Lewy pathology (LP) and neuronal death are commonly found in the brains of patients with clinical Parkinson disease (cPD). It is widely believed that LP appears early in the disease and spreads in synaptically coupled brain networks, driving neuronal dysfunction and death. However, post-mortem analysis of human brains and connectome-mapping studies show that the pattern of LP in cPD is not consistent with this simple model, arguing that, if LP propagates in cPD, it must be gated by cell- or region-autonomous mechanisms. Moreover, the correlation between LP and neuronal death is weak. In this Review, we briefly discuss the evidence for and against the spreading LP model, as well as evidence that cell-autonomous factors govern both α-syn pathology and neuronal death.
摘要
在临床帕金森病（cPD）患者的大脑中，通常会发现细胞内富含α-突触核蛋白（α-syn）的蛋白聚集体，即路易氏病理（LP），以及神经元死亡。人们普遍认为，LP在疾病早期出现，并在突触连接的脑网络中扩散，导致神经元功能障碍和死亡。然而，对人类大脑的尸检分析和连接组映射研究表明，cPD中LP的模式与这个简单模型不一致，这表明，如果LP在cPD中传播，它必须受到细胞或区域自主机制的控制。此外，LP与神经元死亡之间的相关性较弱。在这篇综述中，我们简要讨论了支持和反对LP传播模型的证据，以及细胞自主因素控制α-syn病理和神经元死亡的证据。
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