Abstract

Mutations in LRRK2 (leucine-rich repeat kinase 2) represent a significant component of both sporadic and familial PD (Parkinson's disease). Pathogenic mutations cluster in the enzymatic domains of LRRK2, and kinase activity seems to correlate with cytotoxicity, suggesting the possibility of kinase-based therapeutic strategies for LRRK2-associated PD. Apart from cytotoxicity, changes in autophagy have consistently been observed upon overexpression of mutant, or knockdown of endogenous, LRRK2. However, delineating the precise mechanism(s) by which LRRK2 regulates autophagy has been difficult. Recent data suggest a mechanism involving late steps in autophagic-lysosomal clearance in a manner dependent on NAADP (nicotinic acid-adenine dinucleotide phosphate)-sensitive lysosomal Ca2+ channels. In the present paper, we review our current knowledge of the link between LRRK2 and autophagic-lysosomal clearance, including regulation of Ca2+-dependent events involving NAADP.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.