Parkinson's Disease Mechanisms and Treatments

The paper develops and validates a multiplexed mass spectrometry assay to quantify LRRK2-phosphorylated Rab proteins and biomarker sites, showing VPS35[D620N] enhances Rab1 phosphorylation in Parkinson's disease.

The paper shows that α-synuclein forms liquid droplets that mature into amyloid-rich hydrogels, suggesting Lewy body formation is linked to arrested maturation in the presence of lipids.

The paper analyzes rare SNCA variation in the UK Biobank cohort, identifying copy number variants but no pathogenic missense variants or PD cases among carriers.

The paper shows that overexpressing TOM20 in rat midbrain neurons prevents α-synuclein-induced dopaminergic neurodegeneration by restoring mitochondrial protein import.

This study shows that a selective D1 dopamine agonist, dihydrexidine, significantly improves parkinsonian symptoms in severe MPTP-treated non-human primates where levodopa is ineffective.

This study examines how L-DOPA affects gene expression in the frontal cortex of rats with unilateral dopaminergic lesions, identifying bilateral gene expression changes and non-specific drug effects.

The paper uses GWAS, PRS, and MR to show a genetic link between Parkinson's disease and CSF Aβ42 and APOE locus.

The paper investigates the role of Spen in glial lipid metabolism and its protective effect against paraquat toxicity in Drosophila.

The paper assesses the association of NUS1 variants with Parkinson's Disease in European descent cohorts and finds no evidence of a link, suggesting previous findings may be due to population-specific variants.

The paper analyzes mitochondria-mitochondria interaction networks in Parkinson's disease and finds altered topological patterns that correlate with clinical scores and can distinguish patients from controls.

This study shows RNF11 knockdown increases dopamine release and uptake in Drosophila, while overexpression has the opposite effect, suggesting RNF11 regulates dopamine neurotransmission.

The paper analyzes copy number variants in Latin American Parkinson's disease patients and finds enrichment of variants overlapping known Parkinson's genes, particularly PARK2, associated with early-onset disease.

The paper examines the association of UQCRC1 variants with Parkinson's disease in Europeans using GWAS and whole-genome sequencing data, finding no significant associations.

This study sequenced five genes in PD patients and controls, finding no significant association with Parkinson's Disease after multiple comparisons.

This study evaluates hand dexterity function in a non-human primate Parkinson's disease model using a hand dexterity task and identifies correlations with tremor symptoms and dopamine transporter levels.

This paper identifies genetic variants associated with cognitive and motor progression in Parkinson's disease using GWAS and longitudinal cohort data.

This study shows α-synuclein increases phosphatidylinositol 4,5-bisphosphate levels to facilitate clathrin-mediated endocytosis and synaptic vesicle recycling.

This study shows that metabolic defects in C. elegans lead to hyperactive mitochondria and Parkinson's-like traits, with metformin improving motor function and reducing neurodegeneration.

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.