LRRK2 impairs PINK1/Parkin-dependent mitophagy via its kinase activity: pathologic insights into Parkinson's disease

• Published in: Human molecular genetics Vol. 28; no. 10; pp. 1645 - 1660
• Main Authors: Bonello, Fiona, Hassoun, Sidi-Mohamed, Mouton-Liger, François, Shin, Yea Seul, Muscat, Adeline, Tesson, Christelle, Lesage, Suzanne, Beart, Philip M, Brice, Alexis, Krupp, Johannes, Corvol, Jean-Christophe, Corti, Olga
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 15.05.2019; Oxford University Press (OUP)
• Subjects: Adult; Aged; Benzodiazepinones - pharmacology; Carbonyl Cyanide m-Chlorophenyl Hydrazone - analogs & derivatives; Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology; Female; Fibroblasts - drug effects; Fibroblasts - pathology; Fluorescence Resonance Energy Transfer; Genetics; Human genetics; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - antagonists & inhibitors; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics; Life Sciences; Male; Middle Aged; Mitochondria - genetics; Mitochondria - pathology; Mitophagy - drug effects; Mutation; Neurobiology; Neurons and Cognition; Parkinson Disease - genetics; Parkinson Disease - pathology; Phosphorylation; Primary Cell Culture; Protein Kinases - genetics; Pyrimidines - pharmacology; Ubiquitin-Protein Ligases - genetics

Abstract Mutations of LRRK2, encoding leucine-rich repeat kinase 2 (LRRK2), are the leading cause of autosomal dominant Parkinson's disease (PD). The most frequent of these mutations, G2019S substitution, increases kinase activity, but it remains unclear how it causes PD. Recent studies suggest...