Application of c-Abl inhibitors in the treatment of Parkinson′s disease

VernacularTitle:c-Abl抑制剂应用于治疗帕金森病的进展研究
Author: Xiaoyan MA
Keywords: Parkinson's disease; c-Abl; Inhibitors; A-synuclein; Nilotinib; Ieukemia
From: Journal of Medical Postgraduates 2017;30(6):653-656
CountryChina
Language:Chinese
Abstract: Parkinson's disease (PD) is a common neurodegenerative disorder associated with aging.Recent studies in animal models of PD and analyses of brain specimen from PD patients revealed an increase in the level and activity of the non-receptor tyrosine kinase Abelson (c-Abl) in dopaminergic neurons with phosphorylation of protein substrates,such as a-synuclein and the E3 ubiquitin ligase, Parkin.Most significantly inhibition of c-Abl kinase activity by small molecular compounds used in the clinic to treat human leukemia has shown promising neuroprotective effects in cell and animal models of PD.This has raised hope that similar beneficial outcome may also be observed in the treatment of PD patients by using c-Abl inhibitors.Here we highlight the background for the current optimism, reviewing c-Abl and its relationship to pathophysiological pathways prevailing in PD, as well as discussing issues related to the pharmacology and safety of current c-Abl inhibitors.Clearly more rigorously controlled and well-designed trials are needed before the c-Abl inhibitors can be used in the neuroclinic to possibly benefit an increasing number of PD patients.