Inhibition of LRRK2 or Casein Kinase 1 Results in LRRK2 Protein Destabilization.

ABSTRACT: Mutations and variations in the leucine-rich repeat kinase 2 (LRRK2) gene are strongly associated with an increased risk to develop Parkinson's disease (PD). Most pathogenic LRRK2 mutations display increased kinase activity, which is believed to underlie LRRK2-mediated toxicity. Therefore, major efforts have been invested in the development of potent and selective LRRK2 kinase inhibitors. Several of these compounds have proven beneficial in cells and in vivo, even in a LRRK2 wild-type background. Therefore, LRRK2 kinase inhibition holds great promise as disease-modifying PD therapy, and is currently tested in preclinical and early clinical studies. One of the safety concerns is the development of lung pathology in mice and non-human primates, which is most likely related to the strongly re

SUBMITTER: De Wit T 

PROVIDER: S-EPMC6657425 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature