Parkinson's Disease Mechanisms and Treatments

Neuron-Specific DNA Methylation Differences in the Prefrontal Cortex in Parkinson's Disease

This study identifies neuron-specific DNA methylation changes in Parkinson's disease prefrontal cortex, revealing hypermethylation at seven novel loci and highlighting the importance of cell-type-specific analysis.

Interplay Between Retroviral Element De-repression and Wnt/β-Catenin Pathway in Cellular Models of Parkinson's Disease

This study shows that 6-OHDA induces HERV-K activation in PD models, which is reduced by Wnt/β-catenin pathway modulation.

Comparative Proteomic Analysis of Environmental and Genetic Models of Parkinsons Disease Highlights the Role of Purine Metabolism.

This study compares proteomic and metabolomic changes in genetic and environmental Parkinson's disease models, identifying purine metabolism as a shared pathway involved in neurotoxicity.

Multi-omics dissection of Parkinson's patient subgroups associated with motor and cognitive severity

The paper uses multi-omics data to identify molecular factors associated with motor and cognitive severity in Parkinson's disease and stratifies patients into subgroups with distinct severity profiles.

Unraveling the Core: Hub Genes Bridging Familial and Sporadic Parkinson's Disease

This study identifies twelve hub genes involved in membrane trafficking and vesicle-mediated transport that are dysregulated in both familial and idiopathic Parkinson's disease and show potential as therapeutic targets.

Pharmacologic NLRP3 Inhibition Modulates Parkinson's Disease-Associated Microglial Transcriptomic Signatures and Mitigates α-Synuclein-Triggered Neurodegeneration

This study evaluates dapansutrile, an NLRP3 inhibitor, in preclinical models of Parkinson's disease and multiple system atrophy, showing improved motor function, reduced neurodegeneration, and transcriptomic changes in microglia.

Multi-cohort, cross-species urinary proteomics reveals signatures of LRRK2 dysfunction in Parkinsons disease

The paper identifies urinary protein signatures linked to LRRK2 dysfunction in Parkinson's disease using multi-cohort proteomics and machine learning, showing cross-species relevance and potential as pharmacodynamic markers.

Machine learning-based image analysis of Parkinson's disease iPS-derived neurons predicts genotype and reveals mitochondria-lysosome abnormalities

The paper uses machine learning to analyze neuronal morphology in Parkinson's disease iPSC-derived neurons, identifying genotype-specific mitochondrial and lysosomal abnormalities.

Evaluating ANO6 as a Parkinson's disease candidate gene: a human genetic investigation of common and rare variant associations

This study investigates ANO6's role in Parkinson's disease by analyzing common and rare variants across large datasets, finding no strong genetic association.

EEG dynamics in Lewy body diseases is related to clinical fluctuations and degeneration of locus coeruleus

This study examines neuronal avalanches in Lewy body diseases, finding increased brain dynamics flexibility linked to clinical symptoms and degeneration of the locus coeruleus.

The Vesicular Glutamate Transporter Modulates Sex and Region-Specific Differences in Dopaminergic Neuron α-Synuclein Toxicity by Modifying Cytosolic Dopamine Levels

This study shows that lower vesicular glutamate transporter levels in dopamine neurons increase cytosolic dopamine, leading to mitochondrial dysfunction and increased α-synuclein A53T toxicity in female flies.

LRRK2 I1371V Impairs Astrocytic Glucose Metabolism and Triggers Multi-Organellar Dysfunction in PD

This study shows that the LRRK2-I1371V mutation impairs astrocytic glucose metabolism and causes multi-organellar dysfunction in Parkinson's disease.

Identification of Pesticides Associated with an Increased Risk of Parkinson's Disease using a Multi-Screen Approach

This study identifies six pesticides linked to increased Parkinson's disease risk through three screens and in vivo testing in zebrafish.

Concentration-Dependent Mutational Scanning Probes the Cellular Folding Landscape of α-Synuclein in Yeast

This study uses deep mutational scanning in yeast to show that α-synuclein misfolding and toxicity are concentration-dependent, with mutations altering membrane binding affinity and folding equilibrium.

Astrocytic lysosome deficits reduce alpha-synuclein degradation and induce spread of pathology

This study shows that astrocytic lysosome deficits impair alpha-synuclein degradation and promote its pathological spread in Parkinson's Disease.

Comparative analysis of T-cell signatures and astroglial reactivity in Parkinson's pathology across animal models with distinct regenerative capacities

This study compares T-cell signatures and astroglial reactivity in Parkinson's disease across animal models with different regenerative capacities, finding species- and model-specific immune profiles.

In vivo Proximity & Spatial Proteomics with CRISPR Screening Identify STXBP1 as a Protective Modifier of a-synuclein Toxicity in Dopamine Neurons.

The paper uses in vivo proteomics and CRISPR screening to identify STXBP1 as a protective factor against α-synuclein toxicity in dopamine neurons in Parkinson's disease models.

Single-cell multiomics identifies both shared and unique features of immune dysfunction in Parkinson's disease and inflammatory bowel disease colon, plasma and stool

The paper uses single-cell multiomics to identify shared and unique immune dysfunction features in Parkinson's disease and inflammatory bowel disease across gut, plasma, and stool samples.

Novel mitochondrial variants associated with Parkinson's disease reveal a high heteroplasmy-weighted polygenic risk score in Brazilians

The paper identifies mitochondrial variants associated with Parkinson's disease in Brazilians and develops a polygenic risk score linked to increased disease risk.

LRRK2 regulates ArfGAP1 membrane localization, activity and neuronal toxicity via phosphorylation within its lipid-sensing ALPS2 motif

This paper investigates how LRRK2 phosphorylates ArfGAP1, affecting its localization, activity, and toxicity in neurons, with implications for Parkinson's disease.

Environmental Toxin Rotenone Drives LRRK2-Mediated Microtubule, Cilia and Proteostasis Disruption in Parkinson's Disease Model

This study shows rotenone induces phospho-signaling changes in neural cells, which are mediated by Lrrk2, affecting microtubules, cilia, and proteostasis in Parkinson's disease.

Disulfide engineering reveals unexpected pro- and anti-aggregation conformers of human α-synuclein

This study uses disulfide engineering to identify pro- and anti-aggregation conformers of human α-synuclein, revealing previously unknown polymorphs and their functional impacts.

Myeloid PINK1 represses mtDNA release and immune signaling that impacts neuronal pathology in patient-derived idiopathic PD models

This study shows that PINK1 in myeloid cells represses mtDNA release and immune signaling, which contributes to neuronal pathology in Parkinson's disease models.

Grey matter microstructural alterations distinguish cognitive impairment in Lewy body diseases

The paper identifies grey matter microstructural changes in Lewy body diseases using diffusion MRI metrics, finding increased tODI and FWF linked to cognitive impairment and p-tau217 levels.

Neuronal titration of Snca via enhancer disruption mitigates disease onset in a Parkinson's disease mouse model

This study shows that disrupting a Snca enhancer in mice reduces Snca expression and protects against Parkinson's disease pathology and motor impairments.

Differences in stimulus evoked electroencephalographic entropy reduction distinguishes cognitively normal Parkinson's disease participants from healthy aged-matched controls

The paper identifies differences in stimulus-evoked EEG entropy reduction between cognitively normal Parkinson's disease patients and healthy controls, suggesting impaired cognitive function.

Carriers of LRRK2 pathogenic variants show a milder, anatomically distinct brain signature of Parkinsons disease

This study examines how LRRK2 pathogenic variants affect brain structure in Parkinson's disease patients and non-manifesting carriers, finding milder cortical atrophy in LRRK2 PD patients and no atrophy in carriers.

Multiomic Analysis Reveals Molecular Pathways Associated with Intestinal Aggregation of α-Synuclein

This study identifies dopamine production as critical for nitrite-induced α-synuclein aggregation in enteroendocrine cells, showing that benserazide inhibits aggregate formation.

Shared and Sex-Specific Genetic Risk for Parkinson's Disease Risk Across European Populations

This study identifies sex-specific genetic risk factors for Parkinson's disease using GWAS across European populations, finding shared and distinct loci between males and females.

Type-I interferons drive the gastrointestinal inflammatory response in a mouse model of Parkinsons disease

This study shows type-I interferons drive gastrointestinal inflammation in a mouse model of Parkinson's disease, linking gut-brain pathology progression.