抑制α-突触核蛋白聚集化合物的研究进展

Research progress of inhibiting α-synuclein aggregation compounds

帕金森氏症(PD)是人类一种常见的神经系统疾病。目前,对于其致病机制虽不能完全阐明,但已发现其与黑质致密部中的多巴胺能神经元的变性缺失以及脑中细胞质的路易小体(LBs)的形成密切相关。研究发现,聚集的α-突触核蛋白(α-Syn)是LBs的主要成分,与PD的发病机制相关。传统治疗PD药物大多是针对多巴胺的缺失,虽可以缓解PD的症状却不能阻止PD发病进程。鉴于α-Syn在PD发病机制中的关键作用,以α-Syn作为PD研究的全新靶点,对α-Syn聚集的病理过程进行干预,这对PD的早期诊断和治疗有着重要意义。本文对近年来可抑制α-Syn聚集的化合物的研究进展进行综述,以期为相关化合物的发现及合成提供参考。

Parkinson′s disease(PD)is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic neurons in the substantia nigra.Although the etiology of PD is incompletely understood, but considerable evidence suggests that the pathogenesis of PD is closely related to the formation of cytoplasmic Lewy bodies(LBs)in the brain.With the identification of aggregated α-synuclein(α-Syn)species as the main protein constituent of LBs, α-Syn has been considered as one of the major therapeutic targets in the pathogenesis of PD.The currently approved therapies for PD are mainly targeted on the degermation of dopaminergic neurons.Clinical results turned out that this type of therapy may relieve temporary clinical symptoms to some extent, however, it cannot prevent the progression of PD.It is reasonable to infer that α-Syn is a key hallmark of PD.α-Syn will be great significance for the early diagnosis and treatment of PD by intervening the pathological process of α-Syn aggregation.In this article, the recent developments on the molecules that inhibit the formation of α-Syn fibrils as well as the research progress of α-Syn are reviewed.Understanding these compounds which inhibit the aggregation of α-Syn may inform future studies aiming to develop related drug research and development.