LRRK2 inhibition does not impart protection from α-synuclein pathology and neuron death in non-transgenic mice.

ABSTRACT: 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-tolerat

SUBMITTER: Henderson MX 

PROVIDER: S-EPMC6391792 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature