Selective neuronal vulnerability in Parkinson disease.

Selective neuronal vulnerability in Parkinson disease.
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帕金森病的选择性神经元脆弱性。

DOI:
10.1038/nrn.2016.178
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发表时间:
2017-01-20
期刊:
Nature reviews. Neuroscience
影响因子:
--
通讯作者:
Halliday GM
Halliday GM
中科院分区:
其他
文献类型:
--
作者:
Surmeier DJ;Obeso JA;Halliday GM

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细胞内富含α-突触核蛋白(α-syn)的蛋白聚集体称为路易病理(LP)和神经元死亡,常见于临床帕金森病(cPD)患者的大脑。人们普遍认为,LP在疾病早期出现,并在突触偶联的脑网络中扩散,导致神经元功能障碍和死亡。然而,人类大脑的死后分析和连接体映射研究表明,LP在cPD中的模式与这个简单的模型不一致,认为如果LP在cPD中传播,它一定是由细胞或区域自治机制控制的。此外,LP与神经元死亡的相关性较弱。在这篇综述中,我们简要讨论了支持和反对扩张性LP模型的证据,以及细胞自主因子控制α-syn病理和神经元死亡的证据。
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.
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