Parkinson's Disease Mechanisms and Treatments

This study identifies a significant genetic correlation between Parkinson disease and melanoma, highlighting shared genes and pathways.

The paper demonstrates that alpha-synuclein aggregates spread interneuronally in an organotypic hippocampal slice model, independent of serine 129 phosphorylation.

The paper uses an agent-based model to simulate neurodegenerative disease spread, showing how local vulnerability and network connectivity drive Parkinson's disease progression.

This study identifies small molecules that target the intrinsically disordered ensemble of α-synuclein, showing they can inhibit misfolding, restore phagocytosis, and block cellular transmission of α-synuclein.

Across 37,688 Parkinson's cases, 18,618 proxy-cases and 1.4M controls, 90 risk signals map to 78 loci (37 new); an 1805-variant polygenic score explains 26-36% of heritability.

This study investigates the long-term effects of PFE-360 treatment in an AAV-α-synuclein rat model to assess its potential as a LRRK2 inhibitor for Parkinson's disease.

This study conducts a GWAS of Parkinson disease in Spain, identifies a novel population-specific signal at PARK2 associated with age-at-onset, and highlights genetic substructure for future fine-mapping.

This paper applies Mendelian randomization to identify causal factors for Parkinson's disease using 5,839 exposures and reports twelve causal associations, including adiposity.

This study shows that enriched environments reduce inflammation markers in Parkinson's disease mice by altering gut bacteria.

This study stabilizes α-synuclein oligomers using formaldehyde, preserving their structure and function for use as biomarkers in Parkinson's disease research.

This study shows that necroptosis mediates axonal degeneration in Parkinson's disease, suggesting it as a targetable pathway.

This study uses Mendelian randomization to investigate causal links between risky behaviors and Parkinson's disease in over a million participants, finding protective and risk associations for specific behaviors.

This study shows that dopaminergic medication in Parkinson’s disease reduces striatal sensitivity to negative outcomes during learning and affects subsequent approach/avoidance behavior.

The paper shows that Parkinson's disease is associated with systemic inflammation and bacterial proteases, linking them to hypercoagulation and proinflammatory cytokines.

This study shows that dopamine replacement in Parkinson’s disease patients reduces risk aversion in a value-independent manner, while also increasing sensitivity to expected values.

The paper investigates how stress-induced phospho-ubiquitin formation leads to parkin degradation through oxidative and non-oxidative pathways, potentially contributing to Parkinson's disease.

This study uses long-read sequencing to analyze SNCA transcripts in synucleinopathies, revealing new insights into alternative splicing and structural variants.

The paper uses high-resolution imaging and biophysical methods to show that Lewy pathology in Parkinson's disease consists mainly of a crowded membranous medley of vesicles and dysmorphic organelles, with only a small fraction containing proteinaceous filaments.

This study shows phospholipid bilayers catalyze α-synuclein aggregation from monomers, with efficiency depending on membrane composition and leading to dissociable aggregates.

The paper introduces a new parameter, VS, to detect bradykinesia in Parkinson's disease patients using the BRAIN tap test and validates its reliability across different hardware platforms.

This study develops a new Parkinson's disease mouse model showing that reducing α-synuclein aggregates rescues dopamine neuron dysfunction and death.

The paper correlates peripheral mitochondrial function with clinical severity in idiopathic Parkinson’s disease, finding stronger correlations with non-dopaminergic signs and reversible mitochondrial defects under metabolic stress.

This study connects Parkinson’s disease heritability to cell-type-specific gene regulation, finding enrichment in lysosomal genes in astrocytic and microglial subtypes rather than specific cell types or brain regions.

This paper identifies differentially expressed microRNAs in Parkinson’s disease through meta-analyses of multiple datasets, finding significant associations in brain and blood samples.

This study conducts a GWAS to identify genetic determinants of Parkinson's disease age of onset, finding associations with SNCA, TMEM175, and GBA, and highlighting alpha-synuclein's role in disease onset.

This study estimates the heritability of dementia with Lewy bodies (DLB) and finds it to be higher than previous estimates, with low variance explained by polygenic risk scores from Parkinson's or Alzheimer's disease.

The paper classifies Parkin variants into functional groups based on their impact on mitophagy and stability, revealing potential therapeutic targets for Parkinson’s disease.

This study shows that LRRK2 modifies α-syn aggregation and spread in both mouse and human models, suggesting potential therapeutic targets for Parkinson's disease.

This study shows that loss of one Engrailed1 allele in mice increases α-synuclein aggregation after PFF injection, suggesting a role for En1 in PD pathology.