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RedOx regulation of LRRK2 kinase activity by active site cysteines
Mutations of the human leucine-rich repeat kinase 2 (LRRK2) have been associated with both, idiopathic and familial Parkinson’s disease (PD). Most of...
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G2019S selective LRRK2 kinase inhibitor abrogates mitochondrial DNA damage
Pathogenic mutations in LRRK2 cause Parkinson’s disease (PD). The G2019S variant is the most common, which results in abnormally high kinase...
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Perspective on the current state of the LRRK2 field
Almost 2 decades after linking LRRK2 to Parkinson’s disease, a vibrant research field has developed around the study of this gene and its protein...
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Phosphorylation of AQP4 by LRRK2 R1441G impairs glymphatic clearance of IFNγ and aggravates dopaminergic neurodegeneration
Aquaporin-4 (AQP4) is essential for normal functioning of the brain’s glymphatic system. Impaired glymphatic function is associated with...
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Effect of LRRK2 protein and activity on stimulated cytokines in human monocytes and macrophages
Leucine-rich-repeat kinase 2 (LRRK2), a potential therapeutic target for the treatment of Parkinson’s disease (PD), is highly expressed in monocytes...
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LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression
BackgroundMutations in leucine-rich repeat kinase 2 ( LRRK2 ) are the most common cause of familial Parkinson’s disease (PD). These mutations elevate...
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Inhibition of LRRK2 kinase activity rescues deficits in striatal dopamine physiology in VPS35 p.D620N knock-in mice
Dysregulation of dopamine neurotransmission profoundly affects motor, motivation and learning behaviors, and can be observed during the prodromal...
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Proteome wide association studies of LRRK2 variants identify novel causal and druggable proteins for Parkinson’s disease
Common and rare variants in the LRRK2 locus are associated with Parkinson’s disease (PD) risk, but the downstream effects of these variants on...
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Single molecule array measures of LRRK2 kinase activity in serum link Parkinson’s disease severity to peripheral inflammation
BackgroundLRRK2-targeting therapeutics that inhibit LRRK2 kinase activity have advanced to clinical trials in idiopathic Parkinson’s disease (iPD)....
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A Complex Interplay of DJ-1, LRRK2, and Nrf2 in the Regulation of Mitochondrial Function in Cypermethrin-Induced Parkinsonism
Cypermethrin impairs mitochondrial function, induces redox imbalance, and leads to Parkinsonism in experimental animals. Knockdown of deglycase-1...
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Alterations in the LRRK2-Rab pathway in urinary extracellular vesicles as Parkinson’s disease and pharmacodynamic biomarkers
Expression or phosphorylation levels of leucine-rich repeat kinase 2 (LRRK2) and its Rab substrates have strong potential as disease or...
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A potential patient stratification biomarker for Parkinson´s disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells
Parkinson´s disease (PD) is a common neurodegenerative movement disorder and leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target...
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Regulators of proteostasis are translationally repressed in fibroblasts from patients with sporadic and LRRK2-G2019S Parkinson’s disease
Deficits in protein synthesis are associated with Parkinson’s disease (PD). However, it is not known which proteins are affected or if there are...
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Lysosomal Pathogenesis of Parkinson’s Disease: Insights From LRRK2 and GBA1 Rodent Models
The discovery of mutations in LRRK2 and GBA1 that are linked to Parkinson’s disease provided further evidence that autophagy and lysosome pathways...
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LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress
Parkinson’s disease (PD) is a complex multifactorial progressive neurodegenerative disease characterized by locomotor alteration due to the specific...
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The small GTPase Rit2 modulates LRRK2 kinase activity, is required for lysosomal function and protects against alpha-synuclein neuropathology
In Parkinson’s disease (PD) misfolded alpha-synuclein (aSyn) accumulates in the substantia nigra, where dopaminergic neurons are progressively lost....
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LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s disease
Leucine-rich repeat kinase 2 (LRRK2) is a kinase involved in different cellular functions, including autophagy, endolysosomal pathways, and immune...
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Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson’s disease
Elevated urine bis(monoacylglycerol)phosphate (BMP) levels have been found in gain-of-kinase function LRRK2 G2019S mutation carriers. Here, we have...
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Aberrant somatic calcium channel function in cNurr1 and LRRK2-G2019S mice
In Parkinson’s disease (PD), axons of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) degenerate before their cell bodies....
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Pathophysiological evaluation of the LRRK2 G2385R risk variant for Parkinson’s disease
Missense variants in leucine-rich repeat kinase 2 (LRRK2) lead to familial and sporadic Parkinson’s disease (PD). The pathological features of PD...
