Modulation of Parkinson's disease LRRK2 activity and pathogenicity
Basque Center for Biophysics Institute (BIOFISIKA) Leioa, Biscay
Missense mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) cause the majority of familial and some sporadic forms of Parkinson's disease (PD). LRRK2 kinase hyperactivity underlies the pathogenicity of these mutations, and thus inhibition of this enzyme holds promise for the treatment of PD. Potent and specific LRRK2 kinase inhibitors have been reported; however, their safety and therapeutic efficacy remains unestablished. In my seminar I will report the discovery of an essential human micronutrient as a novel class of LRRK2 kinase modulator with a distinct mode of action, which could be harnessed to develop new LRRK2-linked PD therapeutics. Treatment with this micronutrient inhibits LRRK2 kinase activity in cultured cells and brain tissue, and importantly prevents LRRK2 mutant neurotoxicity in animal models of LRRK2-linked PD.
Host: Elena Alberdi