Parkinson's Disease Mechanisms and Treatments

Immune cell distributions in the blood of healthy individuals at high genetic risk of Parkinson's disease

The paper examines immune cell distributions in healthy individuals at high genetic risk of Parkinson's disease and finds no significant associations between polygenic risk scores and immune cell subtypes, though some nominally significant associations were observed.

A FRET-Based FLIM Method to Probe Membrane-Induced Alpha-Synuclein Aggregation in Neurons

The paper develops a FLIM method to study membrane-induced alpha-synuclein aggregation in neurons, providing insights into Parkinson's disease mechanisms.

Unique nigral and cortical pathways implicated by epigenomic and transcriptional analyses in a rotenone rat model of Parkinson's disease

This study identifies region-specific epigenomic and transcriptomic changes in a rotenone rat model of Parkinson's disease, highlighting immune and synaptic dysregulation in the substantia nigra and cortex.

Parkinson's Disease Pathogenic Variants: Cross-Ancestry Analysis and Microarray Data Validation

The paper evaluates the NeuroBooster array's performance in genotyping pathogenic variants in Parkinson's disease across ancestries and validates their frequencies in diverse populations.

Proteomic analysis reveals complex interactions between PERK/ISR and MAPK1 in translational control in a phenotypic toxin model of Parkinsons disease expressing PINTAC peptides.

The paper identifies novel interactions between PERK/ISR and MAPK1 pathways in a Parkinson's disease model using PINTAC peptides, revealing potential therapeutic targets.

Base editing of Ptbp1 in neurons alleviates symptoms in a mouse model for Parkinson's disease

This study uses base editing to downregulate PTBP1 in neurons of a PD mouse model, rescuing motor symptoms without affecting astrocytes.

Mitochondrial oxidant stress promotes alpha-synuclein aggregation and spreading in mice with mutated glucocerebrosidase

This study shows that GBA1 mutations increase mitochondrial oxidative stress, leading to alpha-synuclein aggregation and spreading in a mouse model of Parkinson's disease.

MDSGene update and expansion: Clinical and genetic spectrum of LRRK2 variants in Parkinson's disease

The paper updates and expands the MDSGene database with clinical and genetic data on LRRK2 variants in Parkinson's disease, including 7,885 individuals and 292 variants.

Bidirectional relationship between olfaction and Parkinson's disease

This study identifies genetic correlations between hyposmia and Parkinson's disease, finding a strong causal link from PD to hyposmia but weaker evidence for the reverse.

Understanding the Pathogenicity of Parkin Catalytic Domain Mutants

The paper investigates two pathogenic parkin mutations in the RING2 domain, showing impaired ubiquitin binding and activity through biochemical assays and AlphaFold modeling.

Cortical Complexity Alterations in Motor Subtypes of Parkinson's Disease: A Surface-Based Morphometry Analysis of Fractal Dimension

This study compares cortical complexity and gray matter volume between tremor dominant and postural instability gait difficulty subtypes of Parkinson's disease using surface-based morphometry.

Tipping point in α-synuclein-membrane interactions: stable protein-covered vesicles or amyloid aggregation

This study investigates how lipid membranes influence the equilibrium between free and membrane-bound α-synuclein and its amyloid formation, revealing conditions that promote or inhibit aggregation.

MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity

The paper introduces MJF-14 PLA, a proximity ligation assay for detecting non-inclusion alpha-synuclein aggregates with high specificity and sensitivity, showing pathology precedes Lewy body formation in Parkinson's disease.

Dissecting the differential role of C-terminal truncations in the regulation of aSyn pathology formation and the biogenesis of Lewy bodies

This study investigates how C-terminal truncations of alpha-synuclein (aSyn) affect Lewy body (LB) formation and pathology in Parkinson's disease by analyzing their role in fibril processing and aggregation.

Spontaneous formation of different forms of alpha-synuclein fibrils from a recombinant protein

This study shows that recombinant alpha-synuclein can form different fibril types under the same conditions, and these fibrils can act as seeds to produce similar fibrils.

Synergistic Multi-Pronged Interactions Mediate the Effective Inhibition of Alpha-Synuclein Aggregation by the Chaperone HtrA1

This paper shows how HtrA1* inhibits alpha-synuclein aggregation through synergistic interactions with its PDZ and Protease domains.

The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons

This study investigates the role of cathepsin B in Parkinson's disease by analyzing genetic variants and manipulating catB function in cell models to assess its impact on lysosomal activity and alpha-synuclein clearance.

M4-mediated cholinergic transmission is reduced in parkinsonian mice and its restoration alleviates motor deficits and levodopa-induced dyskinesia

Interpretable machine learning classifiers implicate GPC6 in Parkinson's disease from single-nuclei midbrain transcriptomes

The paper uses machine learning on single-nuclei RNA sequencing data to identify GPC6 as a genetic risk factor for Parkinson's disease.

Decreased SNCA Expression in Whole-Blood RNA Analysis of Parkinson's Disease Adjusting for Lymphocytes

The paper identifies decreased SNCA expression in Parkinson's Disease blood samples after correcting for immune cell effects, suggesting it as a potential transcriptomic biomarker.

Unveiling Peripheral Immune Dysfunction in Parkinson's Disease through Analysis of Blood-based Mitochondrial DNA Copy Number

This study investigates the association between blood mitochondrial DNA copy number and Parkinson's disease, finding that peripheral immune dysfunction, not mitochondrial dysfunction, underlies the observed associations.

Pathogenic LRRK2 mutations cause loss of primary cilia and Neurturin in striatal Parvalbumin interneurons

The paper shows that LRRK2 mutations cause loss of primary cilia and Neurturin in striatal Parvalbumin interneurons, impairing neuroprotective signaling.

Ketone ester-enriched diet ameliorates motor and dopamine release deficits in MitoPark mice

This study shows that a ketone ester-enriched diet improves motor function and dopamine release in MitoPark mice with Parkinson's disease-like symptoms.

The impact of FreeSurfer versions on structural neuroimaging analyses of Parkinson's disease

This study examines how different versions of FreeSurfer affect structural brain measure estimation in Parkinson's disease and shows significant software-induced variability impacting clinical outcomes.

Novel tools to quantify total, phospho-Ser129 and aggregated alpha-synuclein in the mouse brain

The paper develops and validates new immunoassays for quantifying total, phospho-Ser129, and aggregated alpha-synuclein in mouse brain tissue.

Structure of a novel α-synuclein filament fold from multiple system atrophy

The paper determines the structure of a novel α-synuclein filament fold in multiple system atrophy using cryo-EM, identifying a new filament type distinct from other synucleinopathies.

Proteostasis dysregulation in p.A53T-α-Synuclein iPSC-derived astrocytes exacerbates neurodegeneration in a Parkinson's disease model with Lewy-like pathology

This study shows that p.A53T-α-Synuclein astrocytes from Parkinson's patients impair proteostasis, leading to neurodegeneration and Lewy-like pathology in co-cultured neurons.

Mitochondrial dysfunction Impairs the Nuclear Pore Complex in Parkinson's Disease Pathogenesis

The paper investigates how mitochondrial dysfunction affects the nuclear pore complex in Parkinson's disease by analyzing Nup expression and localization in dopaminergic neurons.

Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson's disease overexpressing human alpha-synuclein

Levodopa impairs lysosomal function in sensory neurons in vitro

This study shows high-dose levodopa impairs lysosomal function and reduces lysosomal acidity in sensory neurons, independent of homocysteine effects.