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Mutations in leucine-rich repeat kinase 2 (LRRK2) are one of the most common causes of familial Parkinson's disease (PD). The most common mutations in the LRRK2 gene induce elevated kinase activity of the LRRK2 protein. Recent studies have also suggested that LRRK2 kinase activity may be elevated in idiopathic PD patients, even in the absence of LRRK2 mutations. LRRK2 is therefore a prime candidate for small molecule kinase inhibitor development. However, it is currently unknown how LRRK2 influences the underlying pathogenesis of PD and how LRRK2 might influence extant pathogenesis. To understand whether LRRK2 inhibition would show some benefit in the absence of LRRK2 mutations, we treated a preclinical mouse model of PD with the potent LRRK2 inhibitor MLi-2. The inhibitor was well-tolerated by mice and dramatically reduced LRRK2 kinase activity. However, LRRK2 inhibition did not reverse motor phenotypes, pathological α-synuclein accumulation or neuron loss. The current study suggests that LRRK2 is not necessary for α-synuclein pathogenesis in this mouse model of PD and that further studies are needed to assess the likely clinical benefit of LRRK2 inhibition in idiopathic PD.
Pubmed ID: 30808409 RIS Download
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THIS RESOURCE IS NO LONGER IN SERVICE, documented on February 1st, 2022. Software application for genetic analysis of classical biometric traits like blood pressure or height that are caused by a combination of polygenic inheritance and complex environmental forces. (entry from Genetic Analysis Software)
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets LRRK2 (phospho S935)
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets LRRK2
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets Tyrosine Hydroxylase
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets Prosurfactant Protein C
View all literature mentionsThis monoclonal targets Human alpha Synuclein (phospho S129)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis polyclonal targets Prosurfactant Protein C
View all literature mentionsThis polyclonal targets Prosurfactant Protein C
View all literature mentionsThis polyclonal targets Prosurfactant Protein C
View all literature mentionsThis monoclonal targets LRRK2 (phospho S935)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets Prosurfactant Protein C
View all literature mentionsThis monoclonal targets Human alpha Synuclein (phospho S129)
View all literature mentionsThis monoclonal targets Tyrosine Hydroxylase
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets LRRK2
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets Prosurfactant Protein C
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis polyclonal targets Prosurfactant Protein C
View all literature mentionsThis monoclonal targets Tyrosine Hydroxylase
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets Human alpha Synuclein (phospho S129)
View all literature mentionsThis unknown targets
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets LRRK2 (phospho S935)
View all literature mentionsThis monoclonal targets LRRK2
View all literature mentionsThis unknown targets
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