Xiang Wang, Vitaliy V Bondar ... Anastasia G Henry
Rab12 was identified as a key modulator of LRRK2-dependent Rab phosphorylation that mediates the recruitment of LRRK2 to lysosomes in response to damage.
Martin Steger, Francesca Tonelli ... Matthias Mann
Discovery of a physiological LRRK2 substrate and a new mechanism of Rab regulation should aid Parkinson’s research and the understanding of Rab function.
Bernd K Gilsbach, Franz Y Ho ... Christian Johannes Gloeckner
The Parkinson’s protein Leucine-Rich Repeat Kinase 2 contains a GTPase as well as kinase domain and modulates its intrinsic GTPase activity by autophosphorylation of the P-loop residue threonine 1343.
Chi G Weindel, Samantha L Bell ... Robert O Watson
Long studied in the context of the central nervous system, LRRK2 also functions in peripheral immunity by maintaining mitochondrial homeostasis in macrophages to regulate the type I interferon response.
The most common Parkinson’s disease-associated mutation, LRRK2 G2019S, impairs mitophagy in clinically relevant cells within the mouse brain and this defect can be reversed using a novel LRRK2 inhibitor.
Mattia Volta, Dayne A Beccano-Kelly ... Austen J Milnerwood
LRRK2 G2019S knock-in mice are a genetically faithful model that recapitulates the slow disease progression of familial PD, with initial alterations to behaviour and neurotransmission providing early pathophysiological targets for neuroprotective interventions.
