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LRRK2 has multifaceted roles in zebrafish and that zebrafish represent a complementary model to further our understanding of this central protein
our similar early study and recent confirming experiments using the same reagents reported by Sheng et al. failed to reproduce the phenotype of the loss of dopaminergic neurons, although the mRNA of LRRK2 was molecularly disrupted
results demonstrate that zLRRK2 is an ortholog of hLRRK2 and that the deletion of WD40 domain (show DCAF12L2 Antibodies) of zLRRK2 provides a disease model for PD
Study found elevated LRRK2 levels in CD14 (show NDUFA2 Antibodies)++ and CD16 (show CD16 Antibodies)+ monocyte subsets of Parkinson's disease patients, but not in patients' B-cells; and a dysregulation of monocyte subpopulations was detected in LRRK2 overexpressing mice.
interaction between LRRK2 and PARK16 loci variants do not influence risk of Parkinson's disease.
Pathogenic mutations in LRRK2 comprise the most common cause of familial, late-onset Parkinson's disease, and are found both in hereditary as well as sporadic forms of the disease. (Review)
Study created a conditional LRRK2 G2019S (LRRK2 GS) mutant and a functionally negative control, LRRK2 G2019S/D1994A (LRRK2 GS/DA). Overexpression of LRRK2 GS in mouse forebrain induced behavioral deficits and alpha-synuclein pathology in a kinase-dependent manner.
This study showed that Parkinson disease patients as well as those with LRRK2 mutations present with increased levels of the pro-inflammatory serum markers indicating a common disease status-specific pattern.
The results of this study strengthen the link between LRRK2 and the innate immunity system underscoring the involvement of inflammatory pathways in the neurodegenerative process in Parkinson disease.
we conclude that LRRK2 G2019S mutation most likely originated in a Berber founder who lived at least 5000 years ago.
We discovered a new missense mutation in the LRRK2 gene, c.4321C>A (p.R1441S). LRRK2 p.R1441S represents the fourth pathogenic mutation observed within codon 1441 and its discovery adds to the remarkable complexity of a mutational hotspot within the ROC domain of the LRRK2 protein
The Parkinson's disease-associated LRRK2 mutant G2019S impairs DRD1 (show DRD1 Antibodies) internalization, leading to an alteration in signal transduction. The mutant forms of LRRK2 also affect receptor turnover by decreasing the rate of DRD2 (show DRD2 Antibodies) trafficking from the Golgi complex to the cell membrane.
we have identified a novel genetic association between the autophagy-related LRRK2 gene and susceptibility to SLE.
PD mutation LRRK2 G2019S impairs synaptic vesicle endocytosis in ventral midbrain dopaminergic neurons.
Parkinson's disease-linked LRRK2 mutations increased dendritic and mitochondrial calcium uptake in cortical neurons.
Study found that the transcripts of the Lrrk2 gene in mice, which encodes a multifunctional protein with kinase and GTPase (show RACGAP1 Antibodies) activities, is upregulated only in Inflexible Drinkers suggesting, for the first time, that the Lrrk2 pathway plays a major role in the compulsive ethanol intake behaviour of addicted subjects.
promotes activation of NLRC4 (show NLRC4 Antibodies) inflammasome during Salmonella Typhimurium infection
LRRK2 negatively regulates the clearance of alphaSYN accompanied by down-regulation of the endocytosis pathway; LRRK2 in microglia may function as the offending molecule responsible for neurodegeneration, in terms of down-regulation of alphaSYN clearance.
In addition to disease modeling, leucine-rich repeat kinase 2 (LRRK2) konckin (KI) mice represent a valuable resource for pharmacological studies.
These results of this study demonstrate that alpha-synuclein inclusion formation in neurons can be blocked and that novel therapeutic compounds targeting this process by inhibiting LRRK2 kinase activity may slow progression of PD-associated pathology.
The findings of this study indicated that the G2019S mutation of LRRK2 imparts a gain-of-abnormal function to striatal spiny projection neurons activity and morphology during a stage of development when activity can permanently modify circuit structure and function.
LRRK2 is expressed in enteric neurons and related to alterations of neuronal peptides and IgA.
show that the LRRK2 sequence and expression patterns are conserved between pig and human
This gene is a member of the leucine-rich repeat kinase family and encodes a protein with an ankryin repeat region, a leucine-rich repeat (LRR) domain, a kinase domain, a DFG-like motif, a RAS domain, a GTPase domain, a MLK-like domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. Mutations in this gene have been associated with Parkinson disease-8.
leucine-rich repeat serine/threonine-protein kinase 2
, leucine-rich repeat kinase 2
, leucine-rich repeat serine/threonine-protein kinase 2-like
, augmented in rheumatoid arthritis 17