Parkinson's Disease Mechanisms and Treatments

This study investigates how LRRK2 mutations affect synaptic structure and function in striatal neurons, revealing pathway-specific changes that may contribute to Parkinson's disease.

Stealth α-synuclein fibrils escape ThT detection, outcompete visible polymorphs, and spread neurodegeneratively in vivo.

The paper screens 12 rare LRRK2 variants in Nigerian Parkinson's patients and controls, finding none present in either group.

This study uses a synuclein-transgenic mouse model to identify molecular changes in early Parkinson's disease before neurodegeneration occurs.

This study uses a multi-scale computational model to show that energy deficiencies and calcium elevation contribute to excitotoxic loss of dopaminergic neurons in Parkinson's disease, with specific therapies halting cell loss.

This study examines the association between heterozygous PRKN variants and Parkinson's disease risk and onset, finding no significant associations.

The paper shows that PRKN mutations impair mitophagy in dopaminergic neurons during a metabolic switch to oxidative phosphorylation.

The paper characterizes 16 α-synuclein conformation-specific antibodies using defined preparations of α-synuclein species, finding none are specific to a single species and many recognize fibrils as well as oligomers.

This study investigates associations between mitochondrial genomic variation and risk of Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP), as well as tau pathology measures in PSP.

This study examines evoked magnetic fields in Parkinson's disease patients, finding delayed latencies linked to medication and motor symptoms rather than cognitive impairment.

This study shows that activating the GDNF/RET signaling pathway prevents Lewy Body pathology in dopamine neurons by blocking α-synuclein aggregation.

The paper investigates environmental and genetic risk factors for Parkinson's disease using UK Biobank data, showing gene-environment interactions and improved prediction with polygenic risk scores.

This study investigates the role of Vglut2 in dopamine neuron plasticity and post-lesional striatal reinnervation, finding that Vglut2 expression can be reactivated in adult neurons to support axonal recovery.

This study shows that LRRK2 activity suppresses protein synthesis in Parkinson's disease, with inhibition restoring normal translation in patient fibroblasts.

This study shows that α-Synuclein seeding in the olfactory bulb leads to altered odor-evoked neural activity in the olfactory system.

The paper investigates how lysosomotropic agents enhance LRRK2-mediated Rab10 phosphorylation under lysosomal stress conditions.

The paper compares neurotoxicity of human A53T and mouse α-synuclein variants, finding mouse aSyn is less toxic due to C-terminal substitutions reducing membrane-induced aggregation and vesicle permeabilization.

This study uses fiber photometry with FRET biosensors to show that D1R signaling is sensitized in Parkinsonian rats but becomes desensitized with L-DOPA treatment, leading to increased dyskinesia.

The paper presents a GWAS locus browser for Parkinson's disease that helps prioritize genes associated with risk variants from multiple GWAS studies.

This study develops a transgenic mouse model expressing human alpha-synuclein in noradrenergic neurons, revealing LC pathology and non-motor PD features.

The paper identifies increased TET2 expression as a driver of epigenetic dysregulation in Parkinson’s disease neurons and shows that reducing Tet2 activity is neuroprotective in mice.

This paper validates serum neurofilament light chain (NfL) as a biomarker for Parkinson's disease progression, showing increased levels in PD patients compared to healthy controls and a longitudinal increase correlating with clinical severity.

The paper identifies peptides that disrupt the LRRK2/PP1 interaction and validates their in vitro and in vivo activity.

The paper identifies SMARCA4 and ERK-ETS signaling as targets for suppressing aging-related dopaminergic degeneration in Parkinson's disease using gene co-expression analysis and Drosophila models.

This study finds that male mice show age-related decline in substantia nigra dopamine neuron firing, while females remain resilient, with increased expression of Parkinson's-related genes in males.

This study shows that DJ-1 deficiency in Drosophila and human cell models of Parkinson's disease increases glycolytic enzyme activity, and that FDA-approved drugs can mitigate PD-related phenotypes by enhancing glycolysis.

The paper shows that different α-synuclein strains cause distinct pathologies by differentially inhibiting proteasome activity through structural differences in their C-terminal regions.

This study investigates how dopamine loss and chronic L-DOPA treatment affect striatal cholinergic interneuron firing rates and ion channel activity, revealing specific molecular adaptations.

The paper examines DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease, finding no significant effect of DNM3 on age at onset but a possible interaction between LRRK2 and VAMP4.