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Associations of cholinergic system integrity with cognitive decline in GBA1 and LRRK2 mutation carriers
In Parkinson’s disease (PD), GBA1- and LRRK2-mutations are associated with different clinical phenotypes which might be related to differential...
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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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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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Neurofilament light chain as a mediator between LRRK2 mutation and dementia in Parkinson’s disease
Elevated neurofilament light chain (NfL) levels have been associated with dementia in idiopathic Parkinson’s disease (iPD). To examine the baseline...
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Homozygous mutation of the LRRK2 ROC domain as a novel genetic model of parkinsonism
BackgroundParkinson’s disease (PD) is one of the most important neurodegenerative disorders in elderly people. Mutations in the leucine-rich repeat...
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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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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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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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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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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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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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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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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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Age-related LRRK2 G2019S Mutation Impacts Microglial Dopaminergic Fiber Refinement and Synaptic Pruning Involved in Abnormal Behaviors
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of autosomal dominant Parkinson’s disease (PD), producing...
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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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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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Aberrant dopamine transporter and functional connectivity patterns in LRRK2 and GBA mutation carriers
Non-manifesting carriers (NMCs) of Parkinson’s disease (PD)-related mutations such as LRRK2 and GBA are at an increased risk for develo** PD....
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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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Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson’s disease
The LRRK2 G2019S pathogenic mutation causes LRRK2-associated Parkinson’s disease (L2PD) with incomplete penetrance. LRRK2 non-manifesting carriers...
