标题:
LDN-73794 Attenuated LRRK2-Induced Degeneration in a Drosophila Parkinson’s Disease Model
作者:
Dejun Yang, Sharmila Das, Loujing Song, Tianxia Li, Jianqun Yan, Wanli W. Smith
关键词:
LRRK2, Parkinson’s Disease, LDN-73794, Kinase Activity, Neuronal Degeneration, Dopamine Neuron, Drosophila Model
期刊名称:
Advances in Parkinson's Disease,
Vol.4 No.3,
July
29,
2015
摘要: Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leucine-rich repeat kinase 2 (LRRK2) cause genetic forms of PD and contribute to sporadic PD as well. Disruption of LRRK2 kinase functions has become one of the potential mechanisms underlying disease-linked mutation-induced neuronal degeneration. To further characterize the pharmacological effects of a reported LRRK2 kinase inhibitor, LDN-73794, in vitro cell models and a LRRK2 Drosophila PD model were used. LDN-73794 reduced LRRK2 kinase activity in vitro and in vivo. Moreover, LDN-73794 increased survival, improved locomotor activity, and suppressed DA neuron loss in LRRK2 transgenic flies. These results suggest that inhibition of LRRK2 kinase activity can be a potential therapeutic strategy for PD intervention and LDN-73794 could be a potential lead compound for developing neuroprotective therapeutics.