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突触核蛋白病:我们的现状和未来方向。

Synucleinopathies: Where we are and where we need to go.

机构信息

Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.

Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.

出版信息

J Neurochem. 2020 May;153(4):433-454. doi: 10.1111/jnc.14965. Epub 2020 Feb 19.

Abstract

Synucleinopathies are a group of disorders characterized by the accumulation of inclusions rich in the a-synuclein (aSyn) protein. This group of disorders includes Parkinson's disease, dementia with Lewy bodies (DLB), multiple systems atrophy, and pure autonomic failure (PAF). In addition, genetic alterations (point mutations and multiplications) in the gene encoding for aSyn (SNCA) are associated with familial forms of Parkinson's disease, the most common synucleinopathy. The Synuclein Meetings are a series that has been taking place every 2 years for about 12 years. The Synuclein Meetings bring together leading experts in the field of Synuclein and related human conditions with the goal of discussing and advancing the research. In 2019, the Synuclein meeting took place in Ofir, a city in the outskirts of Porto, Portugal. The meeting, entitled "Synuclein Meeting 2019: Where we are and where we need to go", brought together >300 scientists studying both clinical and molecular aspects of synucleinopathies. The meeting covered a many of the open questions in the field, in a format that prompted open discussions between the participants, and underscored the need for additional research that, hopefully, will lead to future therapies for a group of as of yet incurable disorders. Here, we provide a summary of the topics discussed in each session and highlight what we know, what we do not know, and what progress needs to be made in order to enable the field to continue to advance. We are confident this systematic assessment of where we stand will be useful to steer the field and contribute to filling knowledge gaps that may form the foundations for future therapeutic strategies, which is where we need to go.

摘要

突触核蛋白病是以富含α-突触核蛋白 (aSyn) 的包涵体积累为特征的一组疾病。该组疾病包括帕金森病、路易体痴呆 (DLB)、多系统萎缩和单纯自主神经衰竭 (PAF)。此外,编码 aSyn (SNCA) 的基因突变 (点突变和重复) 与家族性帕金森病有关,这是最常见的突触核蛋白病。突触核蛋白会议是一个系列会议,每两年举行一次,已经举办了大约 12 年。突触核蛋白会议汇集了突触核蛋白领域和相关人类疾病的领先专家,旨在讨论和推进研究。2019 年,突触核蛋白会议在葡萄牙波尔图郊区的奥菲尔市举行。会议的主题是“2019 年突触核蛋白会议:我们的现状和未来的方向”,汇集了 300 多名研究突触核蛋白病临床和分子方面的科学家。会议涵盖了该领域的许多悬而未决的问题,采用了一种鼓励与会者进行公开讨论的形式,并强调需要开展更多的研究,希望这些研究会为一组目前尚无治愈方法的疾病带来未来的治疗方法。在这里,我们总结了每个会议讨论的主题,并强调了我们所知道的、不知道的和需要取得进展的方面,以便该领域能够继续前进。我们相信,对我们所处位置的这种系统评估将有助于指导该领域,并有助于填补可能为未来治疗策略奠定基础的知识空白,这是我们未来的方向。

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