LRRK2 G2019S promotes astrocytic inflammatory response induced by oligomeric α-synuclein through NF-κB pathway
Objective: Analyzing the mechanism of inflammatory response induced by oligomeric α-synuclein (O-αS) in LRRK2 G2019S mutation astrocytes to provide new targets and ideas for the…Development of potent, orally bioavailable, and highly selective LRRK2 PROTAC® degrader molecules as potential disease modifying therapeutics for Parkinson’s disease
Objective: Report on the pharmacological characteristics of small molecule PROteolysis TArgeting Chimera (PROTAC) molecules designed to induce degradation of leucine rich repeat kinase 2 (LRRK2)…monogenic parkinson´s disease in a chilean cohort
Objective: To describe the minimum prevalence and distribution of monogenic forms of PD in a chilean cohort Background: About 3–5% of Parkinson’s disease (PD) patients…Caveats regarding a family with PD and LRRK2 mutations
Objective: To describe and discuss genetic considerations regarding a kindred with PD cases with similar clinical characteristics, some with identified mutations in the LRRK2 gene…Caffeine Intake Interacts with Gene Variants in Parkinson’s disease
Objective: We investigate interactions of caffeine intake with PD risk variants and determine PD risk estimates in caffeine-drinkers carrying these variants. Background: Caffeine intake reduces…Assessment of variation in α-synuclein seed amplification assay results in the PPMI cohort: Association with hyposmia
Objective: To understand molecular heterogeneity among Parkinson’s disease (PD) patients, and controls based on α-synuclein seed amplification assay (SAA) results. Background: α-synuclein seed amplification assay…Glucocerebrosidase (GCase) activator, Ambroxol, reduces alpha-synuclein serine-129 phosphorylation and oligomers in mutant LRRK2 R1441G mouse brains
Objective: To explore whether inducing brain GCase activity by Ambroxol™ (ABX; a brain-penetrant GCase activator) can reduce a-synuclein (αSyn) serine-129 phosphorylation and oligomer accumulation in…LRRK2 G2019S as a trigger of inflammatory signaling in patient-derived microglia
Objective: This study explores the inflammatory processes in leucine-rich repeat kinase 2 (LRRK2)- microglia carrying the G2019S mutation and determines their contribution to Parkinson’s disease…Differential Rab10 & Rab8A phosphorylation by LRRK2 variants G2019S & I1371V manifests differences in membrane fluidity & pathogenicity.
Objective: To evaluate the difference in substrate (Rab8A & Rab10) phosphorylation by LRRK2 variants G2019S & I1371V on membrane fluidity & pathogenicity. Background: LRRK2 is…LRRK2 Inhibition by BIIB122/DNL151 Demonstrates Robust Target and Lysosomal Engagement: Pharmacokinetics, Pharmacodynamics and Safety in Phase 1 and Phase 1b Studies in Healthy and Parkinson’s Participants
Objective: To characterize the pharmacokinetics (PK), pharmacodynamics, safety, and exposure-response (E-R) relationships of BIIB122/DNL151 to inform on clinical dose selection. Background: Increased LRRK2 kinase activity…
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