Parkinson's Disease Mechanisms and Treatments

L-DOPA induces spatially discrete changes in gene expression in the forebrain of mice with a progressive loss of dopaminergic neurons

The paper examines L-DOPA-induced gene expression changes in the forebrain of mice with progressive dopaminergic neuron loss, identifying region-specific effects and novel genes involved in nonmotor PD symptoms.

Mitochondrial complex I deficiency occurs in skeletal muscle of a subgroup of individuals with Parkinson's disease

The paper investigates mitochondrial complex I deficiency in Parkinson's disease muscle biopsies, finding 9% of cases show reduced CI activity without mtDNA abnormalities.

Sex specific effects of environmental toxin-derived alpha synuclein on enteric neuronal-epithelial interactions

This study investigates sex-specific effects of environmental toxin-derived alpha synuclein on enteric neuronal-epithelial interactions in a mouse model of Parkinson's Disease, finding increased aSyn and CGRP immunoreactivity in females.

Midbrain organoids with an SNCA gene triplication display dopamine-dependent alterations in network activity

This study shows that midbrain organoids with SNCA gene triplication exhibit PD-like neural activity changes, which can be reversed by dopamine agonists.

Environmental exposures and familial background alter the induction of neuropathology and inflammation after SARS-CoV-2 infection.

This study shows that SARS-CoV-2 infection synergizes with MPTP to cause neurodegeneration in mice, which is mitigated by vaccination, but not in all genetic backgrounds.

LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons

This study shows that LRRK2 kinase mediates haloperidol-induced motor side effects in striatal neurons, suggesting LRRK2 as a target to reduce antipsychotic side effects.

Lack of association between G6PD variants and Parkinson's disease

This study investigates the association between G6PD variants and Parkinson's disease across six cohorts and finds no significant links for common or rare variants.

Physiological alpha-synuclein S129 phosphorylation mediates postsynaptic and nuclear interactions in the human brain

The paper maps physiological alpha-synuclein S129 phosphorylation interactomes in the human brain and confirms their presence in healthy non-human primates.

Structural insight into binding of novel PET tracer MODAG-005 to lipidic ????-Synuclein fibrils

This study identifies two binding sites of the PET tracer MODAG-005 on lipidic α-synuclein fibrils, with the cavity site being more stable and selectively occupied under certain conditions.

MHCII reduction is insufficient to protect mice from alpha-synuclein-induced degeneration and the Parkinson's HLA locus exhibits epigenetic regulation

The paper investigates the role of MHCII reduction in protecting mice from alpha-synuclein-induced degeneration and finds that it is insufficient, while showing epigenetic regulation of the Parkinson's HLA locus.

Sex-dimorphic effects of neuromelanin buildup in rodent nigral dopamine neurons: implications for sex-biased vulnerability in Parkinson's disease

This study investigates sex-dimorphic effects of neuromelanin buildup in rodent nigral dopamine neurons, revealing sex-biased impacts on neuronal activity, mitochondrial function, and non-motor Parkinson's symptoms.

Live-Cell Quantification Reveals Viscoelastic Regulation of Synapsin Condensates by α-Synuclein

The paper quantifies viscoelastic properties of synapsin condensates in live cells and identifies α-synuclein's role in regulating their material state.

Prioritizing Parkinson's disease risk genes in genome-wide association loci

This paper prioritizes Parkinson's disease risk genes in GWAS loci using a polygenic priority score, identifying 46 genes with potential for therapeutic development.

Targeted degradation of α-synuclein prevents PFF-induced aggregation

This study demonstrates targeted degradation of α-synuclein using a nanobody-guided system, preventing PFF-induced aggregation in neurons.

Alpha-synuclein aggregation and dopaminergic neuron death in a new mouse model of Parkinson disease expressing human full-length and C-terminally truncated 1-120 alpha-synuclein.

This study shows that co-expressing human full-length and C-terminally truncated alpha-synuclein in mice increases alpha-synuclein aggregation and dopaminergic neuron loss, supporting the MI2BACo mouse model as a tool for Parkinson's disease research.

JM-20 administration to animals with lesion of the nigrostriatal dopamine pathway induced by 6-hydroxydopamine, partially reverses motor damage and oxidative stress

JM-20 treatment in 6-OHDA lesioned rats reduces motor asymmetry and oxidative stress markers in the SNpc and striatum.

Single-vesicle tracking of α-synuclein oligomers reveals pore formation by a three-stage model modulated by charge, curvature, lipids and ligands

This study uses single-vesicle tracking to show α-synuclein oligomers form pores through a three-stage process influenced by membrane curvature, charge, lipids, and ligands.

Local ionic conditions modulate the aggregation propensity and influence the structural polymorphism of alpha-synuclein

This study investigates how Ca2+ and Na+ ions affect alpha-synuclein aggregation and fibril polymorphism, revealing their distinct roles in modulating conformational dynamics and structural outcomes.

HSF1 Activator Azadiradione Ameliorates Parkinson Disease and Extends Lifespan in Preclinical Models: Analysis of Underlying Molecular Mechanism

This study shows that azadiradione enhances protein quality control mechanisms and alleviates Parkinson's disease symptoms in preclinical models.

Synaptic deregulation of cholinergic projection neurons causes olfactory dysfunction across 5 fly Parkinsonism models

The paper identifies synaptic dysfunction in cholinergic projection neurons as an early indicator of Parkinsonism across multiple fly models and links it to olfactory dysfunction and dopaminergic decline.

Criterion for assessing accumulated neurotoxicity of alpha-synuclein oligomers in Parkinson's disease

The paper introduces a metric for measuring accumulated neurotoxicity of alpha-synuclein oligomers and finds that rapid fibril formation reduces toxicity, while impaired degradation increases it.

Deciphering shared molecular dysregulation across Parkinson's disease variants using a multi-modal network-based data integration and analysis

The paper integrates multi-modal data to identify shared molecular dysregulation across Parkinson's disease variants, finding common transcriptomic features in glial cells and potential involvement of ROBO signalling.

The role of RNA in the nanoscale organization of alpha-synuclein phase separation

This study investigates how RNA affects alpha-synuclein phase separation, showing RNA induces morphological changes and promotes liquid-to-solid transition.

Released mitochondrial DNA and neurofilament light chain as Parkinson's disease phenotypes in patient-specific midbrain assembloids

The paper assesses mitochondrial DNA and neurofilament light chain levels in midbrain assembloids to identify Parkinson's disease phenotypes and potential biomarkers.

α-Synuclein Activates the PI3K/AKT Pathway to Drive Lipid Droplets Accumulation: Implications for Parkinson's Disease

This study shows that α-synuclein activates the PI3K/AKT pathway, leading to lipid droplet accumulation in Parkinson's disease, and suggests PI3K inhibition as a therapeutic strategy.

RNA sequence analysis of somatic mutations in aging and Parkinson's Disease

The paper analyzes RNA-seq data from Parkinson's Disease patients and controls to find increased somatic mutations in PD, with some clonal mutations being protective.

Spatial mapping of α-synuclein seeding activity and pathology using immunofluorescence-integrated quiescent seed amplification

This paper introduces IF-QSAA, a method that maps alpha-synuclein seeding activity and pathology in tissue, revealing white-matter enrichment and resolving hemispheric asymmetry in Parkinson's disease.

Identification of expanded and interrupted ATXN2 repeat expansions in Parkinson's disease cohorts

The paper screens whole genome sequencing data from PD and LBD cohorts to identify ATXN2 repeat expansions, finding them in cases but not controls.

Prognostic and biological roles of Parkinson's disease genes in cancer

The paper investigates the association between Parkinson's disease genes and cancer outcomes, finding gene-specific survival correlations and links to cancer hallmarks and drug responses.

Investigation of the HLA locus in autopsy-confirmed progressive supranuclear palsy

This study investigates the HLA locus in PSP patients, finding associations between specific HLA alleles and disease risk, suggesting an autoimmune mechanism.