LDN-73794 Attenuated LRRK2-Induced Degeneration in a iDrosophila/iParkinson’s Disease Model

Dejun Yang; Sharmila Das; Loujing Song; Tianxia Li; Jianqun Yan; Wanli W. Smith

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LDN-73794 Attenuated LRRK2-Induced Degeneration in a iDrosophila/iParkinson’s Disease Model

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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.

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《帕金森（英文）》 |2015年第3期|49-58|共10页
作者
Dejun Yang; Sharmila Das; Loujing Song; Tianxia Li; Jianqun Yan; Wanli W. Smith;
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作者单位

Department of Pharmaceutical Sciences;

University of Maryland School of Pharmacy;

Baltimore;

USA;

Department of Physiology and Pathophysiology;

Xi’an Jiaotong University School of Medicine;

Xi’an;

China;

Department of Neurology;

University of Massachusetts Medical School;

Worcester;

USA;

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原文格式 PDF
正文语种 chi
中图分类肿瘤学;
关键词
LRRK2; Parkinson’s; Disease; LDN-73794; Kinase; Activity; Neuronal; Degeneration; Dopamine; Neuron; Drosophila; Model;

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LDN-73794 Attenuated LRRK2-Induced Degeneration in a iDrosophila/iParkinson’s Disease Model

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