"LRRK2: Autophagy and Lysosomal Activity".

Frontiers in Neuroscience
Marta MadureiraRichard Wade-Martins

Abstract

It has been 15 years since the Leucine-rich repeat kinase 2 (LRRK2) gene was identified as the most common genetic cause for Parkinson's disease (PD). The two most common mutations are the LRRK2-G2019S, located in the kinase domain, and the LRRK2-R1441C, located in the ROC-COR domain. While the LRRK2-G2019S mutation is associated with increased kinase activity, the LRRK2-R1441C exhibits a decreased GTPase activity and altered kinase activity. Multiple lines of evidence have linked the LRRK2 protein with a role in the autophagy pathway and with lysosomal activity in neurons. Neurons rely heavily on autophagy to recycle proteins and process cellular waste due to their post-mitotic state. Additionally, lysosomal activity decreases with age which can potentiate the accumulation of α-synuclein, the pathological hallmark of PD, and subsequently lead to the build-up of Lewy bodies (LBs) observed in this disorder. This review provides an up to date summary of the LRRK2 field to understand its physiological role in the autophagy pathway in neurons and related cells. Careful assessment of how LRRK2 participates in the regulation of phagophore and autophagosome formation, autophagosome and lysosome fusion, lysosomal maturation, maintenanc...Continue Reading

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Citations

Mar 23, 2021·The Journal of Cell Biology·Nikhil PanickerTed M Dawson
Mar 27, 2021·Biochemical Society Transactions·Francois Singh, Ian G Ganley
Feb 3, 2021·Molecular and Cellular Biology·Ahsan UsmaniAnnie Hiniker
Jun 26, 2021·Frontiers in Aging Neuroscience·Haigang RenGuanghui Wang
Jun 22, 2021·Journal of Parkinson's Disease·Meir Schechter, Ronit Sharon
Jul 2, 2021·The FEBS Journal·Luis Bonet-Ponce, Mark R Cookson
Aug 28, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yujie TianLi Wu
Sep 9, 2021·Biochemical Society Transactions·Giovanni Piccoli, Mattia Volta
Sep 14, 2021·The Biochemical Journal·Anna TasegianDario R Alessi
Oct 13, 2021·Chemical Society Reviews·Shukun TangQun Wang

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Methods Mentioned

BETA
GTPase
GTPases
transgenic
biopsies
dissection

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