Selective vulnerability in neurodegenerative diseases.

Selective vulnerability in neurodegenerative diseases.
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DOI:
10.1038/s41593-018-0221-2
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发表时间:
2018-10
影响因子:
25
通讯作者:
Duff KE
Duff KE
中科院分区:
医学1区
文献类型:
--
作者:
Fu H;Hardy J;Duff KE

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神经退行性疾病有两个基本特征,我们通常认为它们是理所当然的。第一种是与疾病相关的病理学只影响特定的神经元(“选择性神经元可识别性”);第二种是病理学随着时间的推移而变化,并以刻板和可预测的方式影响更多的区域。支持选择性神经元和区域脆弱性的机制一直难以剖析,但最近的应用全基因组技术,小鼠模型的发展,再现病理学的空间和时间特征,以及脆弱神经元的内在形态,电生理和生化特性的鉴定,开始揭示神经退行性疾病的这些基本特征。在这里,我们详细介绍了我们对选择性神经元脆弱性的基础生物学的新认识,并概述了我们的理解是不完整的一些领域。
Neurodegenerative diseases have two general characteristics that are so fundamental we usually take them for granted. The first is that the pathology associated with the disease only affects particular neurons (‘selective neuronal vulnerability’); the second is that the pathology worsens with time and impacts more regions in a stereotypical and predictable fashion. The mechanisms underpinning selective neuronal and regional vulnerability have been difficult to dissect, but the recent application of whole-genome technologies, the development of mouse models that reproduce spatial and temporal features of the pathology, and the identification of intrinsic morphological, electrophysiological, and biochemical properties of vulnerable neurons are beginning to shed some light on these fundamental features of neurodegenerative diseases. Here we detail our emerging understanding of the underlying biology of selective neuronal vulnerability and outline some of the areas in which our understanding is incomplete.
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