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Li, T., Yang, D., Zhong, S., Thomas, J.M., Xue, F., Liu, J., Kong, L., Voulalas, P., Hassan, H.E., Park, J.S., MacKerell Jr., A.D. and Smith, W.W. (2014) Novel LRRK2 GTP-Binding Inhibitors Reduced Degeneration in Parkinson’s Disease Cell and Mouse Models. Human Molecular Genetics, 23, 6212-6222.

has been cited by the following article:

• TITLE: LDN-73794 Attenuated LRRK2-Induced Degeneration in a Drosophila Parkinson’s Disease Model

  AUTHORS: Dejun Yang, Sharmila Das, Loujing Song, Tianxia Li, Jianqun Yan, Wanli W. Smith

  KEYWORDS: LRRK2, Parkinson’s Disease, LDN-73794, Kinase Activity, Neuronal Degeneration, Dopamine Neuron, Drosophila Model

  JOURNAL NAME: Advances in Parkinson's Disease, Vol.4 No.3, July 29, 2015

  ABSTRACT: 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.