Kostas Vekrellis, Evangelia Emmanouilidou, Maria Xilouri, Leonidas Stefanis
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引用次数: 0
Abstract
α-Synuclein (AS) is a small presynaptic protein that is genetically, biochemically, and neuropathologically linked to Parkinson's disease (PD) and related synucleinopathies. We present here a review of the topic of this relationship, focusing on more recent knowledge. In particular, we review the genetic evidence linking AS to familial and sporadic PD, including a number of recently identified point mutations in the SNCA gene. We briefly go over the relevant neuropathological findings, stressing the evidence indicating a correlation between aberrant AS deposition and nervous system dysfunction. We analyze the structural characteristics of the protein, in relation to both its physiologic and pathological conformations, with particular emphasis on posttranslational modifications, aggregation properties, and secreted forms. We review the interrelationship of AS with various cellular compartments and functions, with particular focus on the synapse and protein degradation systems. We finally go over the recent exciting data indicating that AS can provide the basis for novel robust biomarkers in the field of synucleinopathies, while at the same time results from the first clinical trials specifically targeting AS are being reported.
α-突触核蛋白(AS)是一种突触前小蛋白,在遗传学、生物化学和神经病理学上与帕金森病(PD)和相关的突触核蛋白病有关。我们在此回顾了这一关系,重点是最新的知识。特别是,我们回顾了将强直性脊柱炎与家族性和散发性帕金森病联系起来的遗传学证据,包括最近在 SNCA 基因中发现的一些点突变。我们简要回顾了相关的神经病理学发现,强调有证据表明 AS 的异常沉积与神经系统功能障碍之间存在关联。我们分析了该蛋白质的结构特征,包括其生理和病理构象,特别强调了翻译后修饰、聚集特性和分泌形式。我们回顾了 AS 与各种细胞区系和功能的相互关系,尤其关注突触和蛋白质降解系统。最后,我们将介绍最近的一些令人兴奋的数据,这些数据表明 AS 可为突触核蛋白病领域的新型稳健生物标记物奠定基础,与此同时,首批专门针对 AS 的临床试验结果也正在报告中。
期刊介绍:
Cold Spring Harbor Perspectives in Medicine is a monthly online publication comprising reviews on different aspects of a variety of diseases, covering everything from the molecular and cellular bases of disease to translational medicine and new therapeutic strategies.
Cold Spring Harbor Perspectives in Medicine is thus unmatched in its depth of coverage and represents an essential source where readers can find informed surveys and critical discussion of advances in molecular medicine.