Skvortsova V I, Bachurin S O, Ustyugov A A, Kukharsky M S, Deikin A V, Buchman V L, Ninkina N N
Pirogov Russian National Research Medical University, Ostrovitianov Str., 1, Moscow, 117997, Russia.
Institute of Physiologically Active Compounds of the Russian Academy of Sciences, Severny Dr., Chernogolovka, 1142432, Russia.
Acta Naturae. 2018 Oct-Dec;10(4):59-62.
Uncontrolled protein aggregation, accompanied by the formation of specific inclusions, is a major component of the pathogenesis of many common neurodegenerative diseases known as proteinopathies. The intermediate products of this aggregation are toxic to neurons and may be lethal. The development strategy of pathogenic therapy for proteinopathy is based on the design of drugs capable of both inhibiting proteinopathy progression and increasing the survival of affected neurons. The results of a decade-long research effort at leading Russian and international laboratories have demonstrated that Dimebon (Latrepirdine), as well as a number of its derivatives from a gamma-carboline group, show a strong neuroprotective effect and can modulate the course of a neurodegenerative process in both in vitro and in vivo model systems. The accumulated data indicate that gamma-carbolines are promising compounds for the development of pathogenic therapy for proteinopathies.
不受控制的蛋白质聚集，伴随着特定包涵体的形成，是许多被称为蛋白病的常见神经退行性疾病发病机制的主要组成部分。这种聚集的中间产物对神经元有毒性，可能是致命的。蛋白病致病治疗的发展策略基于能够抑制蛋白病进展并提高受影响神经元存活率的药物设计。俄罗斯和国际领先实验室长达十年的研究成果表明，二甲金刚胺（Latrepirdine）及其γ-咔啉基团的一些衍生物具有很强的神经保护作用，并且在体外和体内模型系统中都可以调节神经退行性过程。积累的数据表明，γ-咔啉是用于开发蛋白病致病治疗的有前景的化合物。
