Parkinson's Disease Mechanisms and Treatments

Using polygenic and transcriptional risk scores to investigate psychiatric and cognitive symptoms in Parkinson's disease

This study uses polygenic and transcriptional risk scores to analyze psychiatric and cognitive symptoms in Parkinson's disease, finding distinct associations between genetic and transcriptional risks and symptom progression.

Dopaminergic Changes in the Subgenual Cingulate Cortex in Dementia with Lewy Bodies Associates with Presence of Depression

The paper investigates dopaminergic and serotonergic changes in the subgenual cingulate cortex of dementia with Lewy bodies patients with and without depression, finding reduced dopaminergic innervation and markers in depressed cases.

Alpha-synuclein knockout impairs melanoma development and alters DNA damage repair in the TG3 mouse model in a sex-dependent manner

This study shows that alpha-synuclein knockout in TG3 mice delays melanoma onset and slows tumor growth, with sex-dependent effects on DNA damage repair.

KCa3.1 Contributes to Neuroinflammation and Nigral Dopaminergic Neurodegeneration in Experimental models of Parkinson's Disease

This study shows that inhibiting KCa3.1 channels reduces neuroinflammation and dopaminergic neurodegeneration in Parkinson's disease models.

Validation of a Mitochondrial Polygenic Score for Parkinson's Disease

The paper validates a mitochondrial polygenic score for Parkinson's disease across diverse populations, finding strong associations in Europeans and Ashkenazi Jews but not in other ancestries.

17q21.31 locus regulates Parkinson's disease relevant pathways through KANSL1 activity

The paper investigates how the 17q21.31 locus influences Parkinson's disease through KANSL1 activity, showing haplotype-specific effects on key biological processes.

Overexpression of alpha synuclein in Midbrain Dopamine Neurons Reduces Dopamine Release Without Cell Loss and Drives Mild Motor Deficits in Mice

Snake venom-inspired novel peptides protect Caenorhabditis elegans against paraquat induced Parkinson's pathology

The paper identifies two novel peptides that protect C. elegans from paraquat-induced Parkinson's-like pathology by inhibiting reactive oxygen species, mitochondrial damage, and alpha-synuclein aggregation.

Novel Parkinson's Disease Genetic Risk Factors Within and Across European Populations

A cross-European Parkinson's disease GWAS meta-analysis of 63,555 cases, 17,700 proxy cases and 1,746,386 controls finds 134 risk loci (59 novel), 157 independent signals, and brain-enriched risk genes.

An In Vivo Model of Alpha-Synuclein Spread from Gut to Brain

This paper develops a zebrafish model to study alpha-synuclein spread from gut to brain, showing progressive neuron loss and pathological changes through endogenous expression and exogenous fibril seeding.

MicroRNAs alteration and unique distribution in the soma and synapses of substantia nigra in Parkinsons disease

The paper identifies miRNA expression changes and distribution in soma and synapses of the substantia nigra in Parkinson's disease and controls.

Anatomical Abnormalities Suggest a Compensatory Role of the Cerebellum in Early Parkinson's Disease

The paper examines longitudinal brain atrophy in early Parkinson's disease and healthy aging, finding accelerated atrophy in PD patients and cerebellar volume changes suggesting compensatory mechanisms.

Molecular and cellular signatures differentiate Parkinson's disease from Parkinson's disease with dementia

This study compares molecular and cellular signatures of Parkinson's disease and Parkinson's disease with dementia using single-nuclear transcriptomics, finding distinct gene expression patterns and biological pathways.

Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson's disease: A DNA co-methylation network analysis

The paper identifies a DNA methylation module in the substantia nigra associated with depressive symptoms in Parkinson's disease.

Dissecting the molecular landscape of Parkinson's disease and Parkinson's disease dementia using highly efficient snRNA-seq (HIF-snRNA-seq)

This study uses HiF-snRNA-seq to analyze the cingulate cortex in Parkinson's disease and Parkinson's disease dementia, identifying cell-type-specific gene expression changes and disease-stage-related pathways.

A long-lived pool of PINK1 imparts a molecular memory of depolarisation-induced activity.

The paper shows that PINK1 accumulates on mitochondria under depolarisation, remains active, and can precondition subsequent PINK1 activation.

An improved polygenic score for Parkinson's disease partly explains variable penetrance of genetic Parkinson's disease

The paper develops an improved polygenic score for idiopathic Parkinson's disease, showing higher discriminative performance and explaining variable penetrance in genetic forms of the disease.

Mapping the peripheral immune landscape of Parkinson's disease patients with single-cell sequencing

This study uses single-cell sequencing to analyze peripheral immune cell changes in Parkinson's disease patients, identifying key immune signatures and potential biomarkers.

Sex-focused analyses of M83 A53T hemizygous mouse model with recombinant human alpha-synuclein preformed fibril injection identifies female resilience to disease progression: A combined magnetic resonance imaging and behavioural study.

The paper investigates sex differences in aSyn pathology progression in M83 mice using MRI and behavioral analysis, finding female resilience to neurodegeneration despite earlier motor symptom onset in males.

Experimental Evidence for Phosphorylation-Driven Allosteric Regulation of Alpha Synuclein Function

This study shows phosphorylated alpha synuclein forms a more stable, compact structure that interacts with VAMP-2 and affects synaptic vesicle dynamics.

Rab27b promotes lysosomal function and alpha-synuclein clearance in neurons

This study shows Rab27b enhances lysosomal function and reduces alpha-synuclein accumulation in neurons, suggesting it as a therapeutic target for synucleinopathies.

Targeting the ClpP-αSynuclein Interaction with a Decoy Peptide to Mitigate Neuropathology in Parkinson's Disease Models

This study develops a decoy peptide, CS2, that disrupts the ClpP-αSynuclein interaction, reducing neuropathology in Parkinson's disease models.

A Novel Mouse Model of Parkinson's Disease for Investigating Progressive Pathology and Neuroprotection

This paper develops a mouse model of Parkinson's disease by overexpressing α-synuclein and demonstrates neuroprotection with PD180970.

Rationally Designed PKD1 Activator Protects Against Neurodegeneration in Pre-clinical Models of Parkinson's Disease

The paper develops a rationally designed PKD1 activator peptide, AK-P4T, which protects against neurodegeneration in pre-clinical Parkinson's disease models.

The 5-HT1F Receptor Agonist Lasmiditan improves Cognition and Ameliorates Associated Cortico-Hippocampal Pathology in Aging Parkinsonian Mice

This study shows that lasmiditan, a 5-HT1F receptor agonist, improves cognition and reduces pathology in aging Parkinsonian mice by enhancing mitochondrial biogenesis and reducing alpha-synuclein aggregation.

Lack of neuroprotection after systemic administration of the soluble TNF inhibitor XPro1595 in an rAAV6-α-Syn+PFFs-induced rat model for Parkinson's disease

This study shows that systemic XPro1595, a TNF inhibitor, does not protect against -Syn-induced Parkinson's-like pathology in rats, despite being effective in other neurodegeneration models.

Exposure to rotenone triggers redox driven systemwide lipidome alterations and metabolic tradeoffs linked to Parkinsons disease

This study examines how chronic rotenone exposure disrupts lipid metabolism and redox balance in Drosophila, linking these changes to Parkinson's disease-like phenotypes.

Cholesterol Dysregulation in APOE4 Astrocytes Promotes α-Synuclein Pathology in miBrains, a Human Brain Tissue Model

This study develops a human brain tissue model (miBrain) to show that APOE4 astrocytes with cholesterol dysregulation promote α-synuclein pathology through endolysosomal dysfunction.

Non-invasive peripheral delivery of CDNF fragment protects neurons in models of Parkinsons and ALS

This paper demonstrates that a novel C-CDNF fragment can protect neurons in Parkinson's and ALS models through non-invasive peripheral delivery.

Molecular rotors provide insight into the mechanism of formation and conversion of α-synuclein aggregates

This study uses molecular rotors to detect and compare oligomer formation and conversion to amyloids in wild-type and two α-synuclein variants, revealing differences in aggregation kinetics.