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…Analysis of α-Synuclein Seed Amplification Assay in Carriers of GBA and LRRK2 Pathogenic Variants
Objective: To assess α-synuclein seed amplification assay (αS-SAA) in cerebrospinal fluid (CSF) from a cohort of PD patients and non-manifesting carriers (NMCs) of pathogenic GBA…Radiological markers of CSF α-synuclein aggregation in Parkinson’s disease patients
Objective: To investigate the association between cerebrospinal (CSF) αS aggregates, MRI, and dopamine transporter spectral tomography (DaTscanTM) imaging metrics. Background: Synuclein amplification assays (SAA) enables…Impairment of SHH signaling in PD LRRK2 I1371V iPSC derived floor plate cells contribute to ontogenic origin of lower dopaminergic-neuron yield
Objective: To estimate SHH responsiveness & signaling of Floor Plate Cells (FPCs) derived from LRRK2 I1371V PD patient-iPSCs along with its link with LRRK2 I1371V…Genetics of Parkinson’s Disease in Polish patients with positive family history-preeliminary study.
Objective: The aim of our study was to find genetic variants associated with the familial forms of Parkinson’s disease (PD) in Polish population. Background: PD…Impaired CaMKII/ERK activation in mouse mutant LRRK2 R1441G fibroblasts was associated with reduced mitochondrial calcium store and efflux in response to depolarization stress
Objective: To determine the molecular link of LRRK2R1441G mutation to impaired CaMKII/ERK signaling under mitochondrial depolarization stress using mutant mouse embryonic fibroblast (MEF) model of…Exploring mitochondrial mechanisms defining Parkinson’s disease penetrance in LRRK2 G2019S neuronal cultures
Objective: We explored mitochondria as integrators of genetics and environment in LRRK2 G2019S neuronal models. Specifically, we aimed to unravel mitochondrial mechanisms that define the…
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