Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein.
Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein.
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DOI：
10.1242/dmm.012146
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发表时间：
2014-01
影响因子：
4.3
通讯作者：
Jackson WS
中科院分区：
文献类型：
--
作者：
Jackson WS
不同神经退行性疾病选择性靶向特定大脑区域的机制是医学上最有趣的谜团之一。例如，众所周知，阿尔茨海默病主要影响大脑中与记忆有关的部分，而帕金森病主要影响大脑中与身体运动有关的部分。然而，其他大脑区域在这些疾病中不受影响的原因尚不清楚。需要更好地了解选择性易感性的现象，以开发特异性保护受影响神经元的靶向治疗方法，从而改变疾病进程并防止其进展。朊病毒疾病是一组令人着迷的神经退行性疾病，因为它们表现出由单个蛋白质的不同序列扰动引起的广泛表型谱。本综述探讨了影响该蛋白的突变可能导致几种不同的神经退行性疾病的途径，以强调选择性易感性的复杂性。本文的前提是，选择性易感性是由特定蛋白质构象和区域特异性微环境的相互作用决定的，这些微环境包含亚细胞成分（如金属、伴侣和蛋白质翻译机制）的独特组合。鉴于在神经退行性过程中有大量潜在的促成因素，更好地了解这些因素如何相互作用将为疾病机制提供宝贵的见解，以指导治疗发现。
The mechanisms underlying the selective targeting of specific brain regions by different neurodegenerative diseases is one of the most intriguing mysteries in medicine. For example, it is known that Alzheimer’s disease primarily affects parts of the brain that play a role in memory, whereas Parkinson’s disease predominantly affects parts of the brain that are involved in body movement. However, the reasons that other brain regions remain unaffected in these diseases are unknown. A better understanding of the phenomenon of selective vulnerability is required for the development of targeted therapeutic approaches that specifically protect affected neurons, thereby altering the disease course and preventing its progression. Prion diseases are a fascinating group of neurodegenerative diseases because they exhibit a wide phenotypic spectrum caused by different sequence perturbations in a single protein. The possible ways that mutations affecting this protein can cause several distinct neurodegenerative diseases are explored in this Review to highlight the complexity underlying selective vulnerability. The premise of this article is that selective vulnerability is determined by the interaction of specific protein conformers and region-specific microenvironments harboring unique combinations of subcellular components such as metals, chaperones and protein translation machinery. Given the abundance of potential contributory factors in the neurodegenerative process, a better understanding of how these factors interact will provide invaluable insight into disease mechanisms to guide therapeutic discovery.
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影响因子：
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