RNA-binding proteins in neurodegeneration: mechanisms in aggregate.
RNA-binding proteins in neurodegeneration: mechanisms in aggregate.
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DOI：
10.1101/gad.304055.117
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发表时间：
2017-08-01
影响因子：
10.5
通讯作者：
Manley JL
中科院分区：
文献类型：
--
作者：
Conlon EG;Manley JL
Conlon和Manley的这篇综述主要关注神经变性中的RNA加工。它描述了神经元如何特别容易受到RNA结合蛋白（RBP）的破坏，导致广泛的神经和神经退行性疾病。神经退化是发达国家的主要死因，也是长寿人群的自然（尽管不幸）后果。尽管对治疗干预的需求很大，但通常情况下，这些疾病在基本分子水平上的了解不够。目前所知甚少的情况促使人们对一种广义的机制线索进行了充满希望的猜测，这种机制线索将这些不同的条件在亚细胞水平上联系在一起，并可用于广泛的治疗益处。在这篇综述中，我们讨论了一系列神经退行性疾病中遗传和病理变化所支持的一个突出理论：神经元特别容易受到RNA结合蛋白剂量和动力学破坏的影响。在这里，我们综合了在临床，遗传和生物物理水平上取得的进展，并得出结论，这一观点为这些神秘的疾病提供了最简洁的解释。在适当的情况下，我们强调疾病专家和RNA生物学家之间的跨学科合作的互惠互利，因为我们设想了一个神经退行性疾病下降和我们对RNA加工的广泛重要性的理解加深的未来。
This review by Conlon and Manley focuses on RNA processing in neurodegeneration. It describes how neurons are particularly vulnerable to disruption of RNA-binding proteins (RBPs), leading to a wide range of neurological and neurodegenerative diseases. Neurodegeneration is a leading cause of death in the developed world and a natural, albeit unfortunate, consequence of longer-lived populations. Despite great demand for therapeutic intervention, it is often the case that these diseases are insufficiently understood at the basic molecular level. What little is known has prompted much hopeful speculation about a generalized mechanistic thread that ties these disparate conditions together at the subcellular level and can be exploited for broad curative benefit. In this review, we discuss a prominent theory supported by genetic and pathological changes in an array of neurodegenerative diseases: that neurons are particularly vulnerable to disruption of RNA-binding protein dosage and dynamics. Here we synthesize the progress made at the clinical, genetic, and biophysical levels and conclude that this perspective offers the most parsimonious explanation for these mysterious diseases. Where appropriate, we highlight the reciprocal benefits of cross-disciplinary collaboration between disease specialists and RNA biologists as we envision a future in which neurodegeneration declines and our understanding of the broad importance of RNA processing deepens.
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影响因子：
15.1
作者：
Baron DM;Kaushansky LJ;Ward CL;Sama RR;Chian RJ;Boggio KJ;Quaresma AJ;Nickerson JA;Bosco DA
通讯作者：
Bosco DA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Arrasate, Montserrat;Finkbeiner, Steven
通讯作者：
Finkbeiner, Steven
影响因子：
2.5
作者：
Azevedo, Frederico A. C.;Carvalho, Ludmila R. B.;Herculano-Houzel, Suzana
通讯作者：
Herculano-Houzel, Suzana
影响因子：
3.5
作者：
Ash, Peter E. A.;Zhang, Yong-Jie;Link, Christopher D.
通讯作者：
Link, Christopher D.