Parkinson's Disease Mechanisms and Treatments

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.

This study develops a rat model of Parkinson's disease caused by the G2019S LRRK2 mutation and shows that kinase and GTPase activities are critical for neurodegeneration.

This paper develops a mouse model expressing aSyn-GFP under native regulatory elements, showing it mirrors endogenous aSyn expression and pathology.

This study shows that dietary amino acid levels modulate LRRK2-induced neurodegeneration in Drosophila and rat neurons by affecting protein synthesis and autophagy.

The paper identifies pathway-specific polygenic risk factors and transcriptomic networks associated with Parkinson disease using large-scale genetic and expression data.

This study investigates the association between GBA variants and risk for isolated REM sleep behavior disorder (iRBD) and conversion to neurodegeneration, finding higher prevalence and increased conversion rates in carriers.

This study investigates lysosomal alterations in PARK2 knockout dopaminergic neurons derived from iPSCs, revealing links between parkin deficiency and lysosomal dysfunction in Parkinson's disease.

This study shows that α-synuclein undergoes liquid-liquid phase separation, which transitions to solid amyloid fibrils, contributing to Parkinson's disease pathogenesis.

This study profiles RNA expression in MSA cerebellar tissue, identifying distinct transcriptional signatures between parkinsonian and cerebellar subtypes, with greater dysregulation observed in the cerebellar subtype.

This study shows that early α-synuclein pathology in a mouse model does not cause mitochondrial respiration deficits in the striatum and amygdala, even under corticosterone-induced hyperactivity.

The paper develops a fluorescent reporter (FluoReSyn) using a nanobody to detect human α-synuclein in cells and tissues, showing its presence in cerebrospinal fluid.

This study examines the synaptic effects of α-synuclein-112, showing it impairs vesicle recycling through enhanced phospholipid binding and oligomerization.

This study determines the structure of α-synuclein filaments in multiple system atrophy using cryo-EM, revealing distinct filament types and conformers that differ from in vitro assemblies.