Parkinson's Disease Mechanisms and Treatments

This study examines how neuronal activity in the dorsolateral prefrontal cortex changes in parkinsonism using nonhuman primates and finds early impairment in task-related firing rates.

This study shows nicotine reduces α-synuclein pathology and behavioral deficits in mice induced by human α-synuclein pre-formed fibrils.

This study shows that α-synuclein aggregates in the motor cortex lead to neuronal hyperexcitability and structural changes, contributing to cortical dysfunction in Parkinson's disease.

The paper investigates shared iron storage and transport deficits in PBMCs from PD and IBD patients, linking them to immune dysfunction and NSAID modulation.

This study shows that systemic administration of a TNF inhibitor does not protect against α-synuclein-induced dopaminergic neuron loss in a rat model of Parkinson's disease.

This study examines how different statins affect the anti-dyskinetic effects of sub-anesthetic ketamine in a rat model of L-DOPA-induced dyskinesia.

The paper investigates genetic interactions between SNCA and APOE in synucleinopathies using GWAS data and finds no significant epistatic interactions after multiple testing correction.

The paper uses atomistic simulations to study how the P1 domain of α-synuclein phase separates with temperature, revealing hydrophobic interactions and the role of tyrosine in condensate formation.

The paper identifies phages in the human substantia nigra and links their presence to Parkinson's Disease pathogenesis through virome analysis and gene expression correlation.

The paper uses NM-sensitive MRI to study neuromelanin accumulation and neurodegeneration in Parkinson's disease models, finding a biphasic signal change linked to a pathogenic threshold.

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.

The paper identifies PINK1 as an autoantigen targeted by T cells in Parkinson's disease, with reactivity predominantly observed in male patients.

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

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.

This study identifies a kinase-dependent negative feedback mechanism regulating LRRK2 Roc G domain activity through autophosphorylation of T1343, affecting GTP hydrolysis kinetics.

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.

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

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.

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.

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.

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.

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.

The paper shows that neurons have constitutive endolysosomal perforations enabling internalized alpha-synuclein fibrils to induce aggregation, and inhibiting PIKfyve kinase reduces this effect.

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.

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

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

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.

The R1441C-LRRK2 mutation leads to age-dependent immune cell exhaustion in macrophages, with sex-specific effects observed in mice and human patients.