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LRRK2 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.
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
This is the first report of LRRK2 I2020T and G2385R GTPase (show RACGAP1 Antibodies) activities and shows that most of the LRRK2 mutations that are pathogenic or a risk factor altered either kinase or GTPase (show RACGAP1 Antibodies) activity, suggesting that their physiological consequences are caused by altered enzyme activities.
The present study demonstrates that MB expression of hLRRK2 in flies recapitulates the clinical features of the sleep disturbances in PD, and that melatonin attenuates hLRRK2-induced sleep disorders and synaptic dysfunction, suggesting the therapeutic potential of melatonin in PD patients carrying LRRK2 mutations.
LRRK2 G2385R genotype may not be associated with cognitive dysfunction in Parkinson's disease.
LRRK2 p.Gly2385Arg can explain most if not all of the PD association at rs1994090 in East Asians, but other nonsynonymous variants are independent.
This study showed that LRRK2, PARK2 (show PARK2 Antibodies) and ATP13A2 (show ATP13A2 Antibodies) are under copy number variations influence in patient with Parkinson disease.
decreased levels of miRNAs targeting LRRK2 might result in a gain of function for LRRK2, and by extension, loss of neuronal viability
Pathogenic LRRK2 variants mapping to different functional domains increase phosphorylation of Rab (show HRB Antibodies) GTPases and this strongly decreases their affinity to regulatory proteins.
Knockdown of either ULK1 (show ULK1 Antibodies) or DLP1 (show DNM1L Antibodies) expression with shRNAs suppresses LRRK2 G2019S expression-induced mitochondrial clearance, suggesting that LRRK2 G2019S expression induces mitochondrial fission through DLP1 (show DNM1L Antibodies) followed by mitophagy via an ULK1 (show ULK1 Antibodies) dependent pathway.
Parkinson disease is likely a pathogenically heterogeneous condition and it suggests the existence of specific mechanisms involved in LRRK2-associated PD.
Asymptomatic carriers of the R1441G-leucine-rich repeat kinase 2 mutation have evidence of dopaminergic nigrostriatal denervation
findings reveal a novel function of LRRK2 in regulating EPO (show EPO Antibodies) expression and imply a potentially novel relationship between PD genes and hematopoiesis.
In the present study demonstrated that the up-regulation of HOTAIR and LRRK2 in the midbrain of PD mice induced by MPTP (show PTPN2 Antibodies).
that mutant LRRK2 may impair synaptic vesicle dynamics via aberrant phosphorylation of N-ethylmaleimide sensitive fusion
14-3-3theta can regulate LRRK2 and reduce the toxicity of mutant LRRK2 through a reduction of kinase activity.
LRRK2 has a role in microglia activation and sustainment of neuroinflammation.
p21-activated kinase 6 (PAK6 (show PAK6 Antibodies)) as a novel interactor of leucine-rich repeat kinase 2 (LRRK2), a kinase involved in Parkinson's disease
The data implicate gain of LRRK2 function in the pathogenesis of Parkinson disease
LRRK2 regulates lysosome size, number and function in primary astrocytes and results show that expression of Parkinson's disease associated LRRK2 variants results in enlarged lysosomes
Present results suggest that LRRK2 may play novel roles in both the immune system and the pathogenesis of various diseases.
Selective expression of Parkinson's disease-related Leucine-rich repeat kinase 2 G2019S missense mutation in midbrain dopaminergic neurons impairs dopamine release and dopaminergic gene expression
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