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


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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Yang, D. , Das, S. , Song, L. , Li, T. , Yan, J. and Smith, W. (2015) LDN-73794 Attenuated LRRK2-Induced Degeneration in a Drosophila Parkinson’s Disease Model. Advances in Parkinson's Disease, 4, 49-58. doi: 10.4236/apd.2015.43007.

Conflicts of Interest

The authors declare no conflicts of interest.


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