Parkinson's Disease Mechanisms and Treatments

This study uses spatial transcriptomics to show that ALDH1A1+ and ALDH1A1- midbrain dopaminergic neurons respond differently to alpha-synuclein overexpression, with distinct transcriptional changes over time.

The paper uses cryo-EM to determine amyloid fibril structures of a truncated alpha-synuclein construct, revealing disease-like motifs without forming the Parkinson's Disease polymorph.

This study identifies microvascular pathology and endothelial proteotoxicity as key features of Progressive Supranuclear Palsy through neuropathological and single-nucleus RNA-sequencing analysis.

This study shows that synucleinopathy triggers complement activation and dysregulation before neurodegeneration in a rat model and human Parkinson's disease tissue.

This study performs an age-stratified meta-analysis of bulk RNA-seq data to identify early and core dysregulated pathways in Parkinson's disease.

This paper describes a rat model of body first Parkinson's disease that replicates motor and non-motor features, including dopaminergic degeneration and alpha-synucleinopathy.

This study shows that overexpressing alpha-synuclein in zebra finch Area X reduces firing rates of specific neurons, mimicking Parkinsonian-like vocal impairments.

This study investigates factors influencing the formation of α-synuclein amyloid fibrils at atomic resolution using cryo-electron microscopy.

This paper develops an RNA aptamer, 1R6, that targets synuclein and shows therapeutic potential in synucleinopathies by inhibiting aggregation and promoting disaggregation.

This study examines how α-synuclein pathology affects T-type calcium currents in vulnerable and resilient dopaminergic neurons in the substantia nigra.

This paper investigates AAV-mediated PRKN gene replacement in Parkin-deficient models to restore mitophagy and demonstrate a feasible gene therapy approach for early-onset Parkinson's disease.

The paper identifies a distal regulatory variant on a shared haplotype that drives neuroinflammatory pathways in GBA1-associated Parkinson's disease, explaining how GBA1 variants increase PD risk.

This study evaluates five anti-α-synuclein single-domain antibodies in Drosophila models, identifying 2H1 as the most effective in reducing pathology and improving disease parameters.

This study uses PSD95 reporter mice to show D1 and D2 MSN synapse loss in PD and LID, identifies microglia-mediated synapse removal, and suggests microglial depletion as a therapeutic target for dyskinesia.

This study shows that dopamine levels influence both neurodegeneration and lifespan in a C. elegans Parkinson's model by modulating -syn toxicity and proteostasis.

The paper investigates how G2019S LRRK2 interacts with metabolic syndrome in a mouse model of Parkinson's disease, showing systemic nucleotide and energy metabolism disruptions and mitochondrial dysfunction.

This study uses correlative light and electron microscopy to analyze Lewy body pathology in Parkinson's and dementia with Lewy bodies, revealing regional differences in ultrastructure and mitochondrial changes.

This study shows that the LRRK2-R1441G mutation causes age-related mitochondrial dysfunction and oxidative stress in dopamine neurons, suggesting calcium channels and uncoupling proteins as therapeutic targets.

The paper performs whole-genome sequencing on Parkinson's Disease cases in India to identify novel pathogenic variants and quantify polygenic risk.

The paper develops an optical screening system to identify small molecules modulating α-synuclein aggregation in cells and finds harman reduces aggregate formation.

This study shows that α-synuclein protofibrils induce tunneling nanotubes in astrocytes, promoting stemness and apoptosis resistance through pFAK-Nanog interaction and p53 degradation.

This study uses single-molecule imaging to show that Parkinson's disease-associated alpha-synuclein aggregates are more stable than physiological multimers under dilution.

This study identifies locus-specific HERV expression patterns in Parkinson's disease patients, revealing shared retroviral signals and immune-related pathway dysregulation across different PD subtypes.

The paper reports the high-resolution SSNMR structure of A30P mutant alpha-synuclein fibrils, showing a conserved Greek key fold not including the mutation site, and validates a method for comparing SSNMR spectra of Asyn polymorphs.

This study investigates the genetic role of SLC7A11 in Parkinson's Disease using whole-genome sequencing data and finds no association between SLC7A11 variants and PD risk or GCase activity.

This study investigates tier-specific vulnerability of dopaminergic neurons in non-human primates by analyzing Lewy body distribution and neuromelanin levels in different brain regions.

This study develops a method to produce highly modified α-synuclein with defined post-translational modifications and a fluorescent label to study their effects on structure and function.

This study identifies plasma protein biomarkers and mechanistic pathways in Parkinson's disease using deep proteomics and functional genomics.