α-突触核蛋白显像剂及小分子抑制剂诊疗药物的研究进展

Progress ofα-synuclein imaging agents and small molecule inhibitors-based theranostics

目的综述α-突触核蛋白(alpha-synuclein,α-syn)的结构及其显像剂和小分子抑制剂的研究进展,为进一步开发新型显像剂提供参考。方法查阅近年来国内外文献,对荧光显像剂、核素示踪剂以及直接或间接靶向α-syn的小分子抑制剂进行归类总结。结果帕金森病(Parkinson′s disease,PD)是第二大进展性神经退行性疾病,与遗传、环境、神经系统老化等因素相关。α-syn聚集而成的不溶性蛋白在脑内沉积以及黑质(SN)中多巴胺神经元(DN)的变性死亡导致了PD的形成。目前,α-syn显像剂的开发仍处于起步阶段,也未能发现具有高特异性的α-syn小分子抑制剂。结论相比于β-淀粉样蛋白(beta-amyloid,Aβ)和tau蛋白等其他类型蛋白,α-syn显像研究进展相对缓慢,但具有良好的发展前景。

Objective This review mainly introduces the structure of alpha-synuclein(α-syn)and its imaging agents and small molecule inhibitors.It provides a reference for the further development of new imaging agents.Methods In this paper,the fluorescent imaging agents,radionuclide tracers and small molecule inhibitors that directly or indirectly targetα-syn are classified and summarized.Results Parkinson′s disease(PD)is the second major progressive neurodegenerative disease,which is related to genetic,environmental and nervous system aging.Insoluble proteins aggregated byα-syn are deposited in the brain,accompanied by dopamine neuron degeneration in the substantia nigra(SN),which leads to the formation of PD.At present,the development ofα-syn imaging agents is still in its infancy,and no highly specificα-syn small molecule inhibitors have been found.Conclusion Compared with other types of protein,such as beta amyloid(Aβ)and tau protein,the progress ofα-syn imaging is relatively slow,but it has good prospects.