Leucine rich repeat kinase knockout (LRRK KO) mouse model: Linking pathological hallmarks of inherited and sporadic Parkinson's disease
Sign Up to like & getrecommendations! Published in 2018 at "Movement Disorders"
DOI: 10.1002/mds.27267
Abstract: Autosomal dominant mutations in Leucine Rich Repeat Kinase 2 (LRRK2) underlie the most common cause of familial Parkinson’s disease (PD) and have also been associated with sporadic cases. However, LRRK2 mutation knockin and LRRK2 knockout… read more here.
Keywords: dko mice; lrrk dko; lrrk; lrrk2 ... See more keywords
LRRK2 Loss‐of‐Function Variants: When Less Is More
Sign Up to like & getrecommendations! Published in 2020 at "Movement Disorders"
DOI: 10.1002/mds.28291
Abstract: Gain-of-function variants in leucine-rich repeat kinase 2 (LRRK2) are the most common monogenic cause of Parkinson’s disease (PD), albeit with incomplete penetrance, indicating that reduction of LRRK2 kinase activity is a reasonable therapeutic strategy for… read more here.
Keywords: lof variants; lrrk2 lof; function variants; lrrk2 ... See more keywords
LRRK2: An Emerging New Molecule in the Enteric Neuronal System That Quantitatively Regulates Neuronal Peptides and IgA in the Gut
Sign Up to like & getrecommendations! Published in 2017 at "Digestive Diseases and Sciences"
DOI: 10.1007/s10620-017-4476-3
Abstract: AbstractBackground Leucine-rich repeat kinase 2 (LRRK2) is a recently discovered molecule associated with familial and sporadic Parkinson’s disease. It regulates many central neuronal functions such as cell proliferation, apoptosis, autophagy, and axonal extension. However, in… read more here.
Keywords: peptides iga; lrrk2 mice; mice; enteric neurons ... See more keywords
The G2019S mutation in LRRK2 imparts resiliency to kinase inhibition
Sign Up to like & getrecommendations! Published in 2018 at "Experimental Neurology"
DOI: 10.1016/j.expneurol.2018.07.012
Abstract: &NA; The G2019S mutation in LRRK2 is one of the most common known genetic causes of neurodegeneration and Parkinson disease (PD). LRRK2 mutations are thought to enhance LRRK2 kinase activity. Efficacious small molecule LRRK2 kinase… read more here.
Keywords: lrrk2 kinase; kinase; g2019s lrrk2; inhibition ... See more keywords
Inhibition of LRRK2 restores Parkin-mediated mitophagy and attenuates intervertebral disc degeneration.
Sign Up to like & getrecommendations! Published in 2021 at "Osteoarthritis and cartilage"
DOI: 10.1016/j.joca.2021.01.002
Abstract: OBJECTIVE To elucidate the role of LRRK2 in intervertebral disc degeneration (IDD) as well as its mitophagy regulation mechanism. METHODS The expression of LRRK2 in human degenerative nucleus pulposus tissues as well as in oxidative… read more here.
Keywords: apoptosis; inhibition; intervertebral disc; lrrk2 ... See more keywords
Sequential screening nominates the Parkinson's disease associated kinase LRRK2 as a regulator of Clathrin-mediated endocytosis
Sign Up to like & getrecommendations! Published in 2020 at "Neurobiology of Disease"
DOI: 10.1016/j.nbd.2020.104948
Abstract: Mutations in leucine-rich repeat kinase 2 (LRRK2) are an established cause of inherited Parkinson's disease (PD). LRRK2 is expressed in both neurons and glia in the central nervous system, but its physiological function(s) in each… read more here.
Keywords: clathrin mediated; kinase lrrk2; disease; parkinson disease ... See more keywords
Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1).
Sign Up to like & getrecommendations! Published in 2017 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.7b01186
Abstract: Mutations in leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated with an increased risk of developing Parkinson's disease. Surrogates for the LRRK2 kinase domain based on checkpoint kinase 1 (CHK1) mutants were designed,… read more here.
Keywords: chk1; leucine rich; kinase; lrrk2 inhibitors ... See more keywords
Molecular Modeling Study on the Interaction Mechanism between the LRRK2 G2019S Mutant and Type I Inhibitors by Integrating Molecular Dynamics Simulation, Binding Free Energy Calculations, and Pharmacophore Modeling.
Sign Up to like & getrecommendations! Published in 2022 at "ACS chemical neuroscience"
DOI: 10.1021/acschemneuro.1c00726
Abstract: Leucine-rich repeat kinase 2 (LRRK2) has been reported in the pathogenesis of Parkinson's disease (PD). G2019S mutant is the most common pathogenic mutation in LRRK2-related PD patients. Inhibition of LRRK2 kinase activity is proposed to… read more here.
Keywords: interaction; hydrogen bond; pharmacophore modeling; lrrk2 ... See more keywords
Evaluation of [18F]PF-06455943 as a Potential LRRK2 PET Imaging Agent in the Brain of Nonhuman Primates.
Sign Up to like & getrecommendations! Published in 2023 at "ACS chemical neuroscience"
DOI: 10.1021/acschemneuro.2c00466
Abstract: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the common causes of inherited Parkinson's disease (PD) and emerged as a causative PD gene. Particularly, LRRK2-Gly2019Ser mutation was reported to alter the early phase… read more here.
Keywords: evaluation 18f; brain; lrrk2; 18f 06455943 ... See more keywords
Leucine-Rich Repeat Kinase 2 (Lrrk2)-Sensitive Na+/K+ ATPase Activity in Dendritic Cells
Sign Up to like & getrecommendations! Published in 2017 at "Scientific Reports"
DOI: 10.1038/srep41117
Abstract: Leucine-rich repeat kinase 2 (Lrrk2) has been implicated in the pathophysiology of Parkinson’s disease. Lrrk2 is expressed in diverse cells including neurons and dendritic cells (DCs). In DCs Lrrk2 was shown to up-regulate Na+/Ca2+-exchanger activity.… read more here.
Keywords: atpase; leucine rich; dendritic cells; rich repeat ... See more keywords
Impact of Type II LRRK2 inhibitors on signaling and mitophagy
Sign Up to like & getrecommendations! Published in 2021 at "Biochemical Journal"
DOI: 10.1042/bcj20210375
Abstract: Much effort has been devoted to the development of selective inhibitors of the LRRK2 as a potential treatment for LRRK2 driven Parkinson's disease. In this study, we first compare the properties of Type I (GSK3357679A… read more here.
Keywords: type lrrk2; impact type; type inhibitors; lrrk2 inhibitors ... See more keywords