Parkinson's Disease Mechanisms and Treatments

A rewiring of the earliest immune events leading to T-cell mediated disease following intestinal infection in a PINK1 knock out mouse model of Parkinsons disease

This study identifies early immune dysregulation in PINK1 KO mice following intestinal infection, showing myeloid cell activation and T cell response as key factors in PD-like disease progression.

Genome-wide assessment identifies novel runs of homozygosity linked to Parkinson's disease etiology across diverse ancestral populations

The paper identifies novel runs of homozygosity linked to Parkinson's disease risk and age at onset across diverse populations using genome-wide data.

Regulation of Leucine-Rich Repeat Kinase 2 by inflammation and IL-4

This study investigates how inflammation and IL-4 regulate LRRK2 expression and activity in immune cells, revealing cell-specific effects and the role of the LRRK2-R1441C mutation.

Repetitive Levodopa Treatment Drives Cell Type-Specific Striatal Adaptations Associated With Progressive Dyskinesia in Parkinsonian Mice

This study shows that repeated levodopa treatment in Parkinsonian mice leads to striatal adaptations, specifically enhanced glutamatergic synapses on D1-MSNs and reduced D2R sensitivity, which contribute to worsening dyskinesia.

Myeloid-Driven Inflammation in Prodromal Parkinson's Disease

The paper identifies increased myeloid-driven inflammation in the CNS of prodromal Parkinson's Disease patients, linking gut and CNS immune responses through shared T cell clones.

Independent Associations of Sleep and Walking with Cognition in Parkinson's Disease: A Perivascular Spaces Analysis

This study examines the relationship between sleep, walking, and cognition in Parkinson's disease, finding that walking difficulties directly impact cognition, while PVS does not mediate these associations.

Multiscale analysis of myelin alterations in skin biopsies from synucleinopathies.

The paper analyzes myelin structure and protein abundance in skin biopsies from synucleinopathy patients to identify structural differences and potential biomarkers.

Using a stable protein scaffold to display peptides that bind to alpha-synuclein fibrils

The paper demonstrates that stable CTPR proteins can be modified to bind alpha-synuclein fibrils with micromolar affinity, enabling the testing of fibril-binding peptides.

A substrate-interacting region of Parkin directs ubiquitination of the mitochondrial GTPase Miro1

This study identifies a conserved region in Parkin that mediates its interaction with Miro1, explaining how Parkin targets and ubiquitinates this mitochondrial GTPase.

Differential memory enrichment of cytotoxic CD4 T cells in Parkinson's disease patients reactive to α-synuclein

The paper investigates T cell subsets in Parkinson's disease patients reactive to α-synuclein, finding reduced Granulysin+ CD4 cytotoxic TEM cells and altered CELSR2 expression.

Synaptic endocytic failure drives dopamine deficiency and protein transfer-mediated striatal dopamine-like neuron compensation

The paper shows that synaptic endocytic failure in dopamine neurons leads to the emergence of dopamine-like neurons through protein transfer, supporting dopamine compensation in early Parkinson's disease.

Predicting Dementia in People with Parkinson's Disease

This study predicts Parkinson's dementia using machine learning and multimodal data, finding genetic predisposition and comorbidities as key factors.

Human- and Rodent-derived Extracellular Vesicles Mediate the Spread of Pathology in MSA-like Models

The paper investigates the role of oligodendroglial-derived extracellular vesicles in spreading pathology in MSA-like models, showing they carry pathological Synuclein and TPPP/p25 and induce disease in animal models.

Retinoid X Receptor as a Therapeutic Target to Treat Neurological Disorders Associated with alpha-Synucleinopathy

This study shows that activating RXR reduces alpha-synuclein pathology and neuroinflammation in a mouse model of Parkinson's disease.

Genome-wide analysis reveals genes mediating resistance to paraquat neurodegeneration in Drosophila

The paper identifies two genes, luna and CG32264, that mediate resistance to paraquat-induced dopaminergic neurodegeneration in Drosophila, with CG32264's mammalian ortholog linked to human Parkinson's disease risk.

Pediococcus pentosaceus decreases α-synuclein accumulation and alleviates parkinsonism in Caenorhabditis elegans and Oryzias latipes

This study shows that Pediococcus pentosaceus reduces α-synuclein accumulation and improves motor function in Parkinson's disease models.

Peripheral immune cell response to stimulation stratifies Parkinson's disease progression from prodromal to clinical stages

The paper stratifies Parkinson's disease stages based on peripheral immune cell responses to stimulation, identifying biomarkers linked to disease progression.

Structural and functional insights into nuclear role of Parkinson's Disease-associated α-Synuclein

This study identifies how Parkinson's Disease-associated α-Synuclein interacts with histone dimers, revealing structural and functional insights into its role in chromatin regulation.

REM sleep predicts reductions in pathophysiological daytime basal ganglia-cortical circuit activity in Parkinson's disease

The paper shows that REM sleep duration and delta activity in Parkinson's disease patients correlate with reduced daytime basal ganglia-cortical network pathology and improved alertness.

The Parkinsons disease associated Leucine-rich repeat kinase 2 affects expression of Transferrin receptor 1 and phosphorylation of key signaling proteins in human iPSC-derived dopaminergic neurons

This study shows that LRRK2 variants affect TfR expression and phosphorylation of GSK-3β and Akt in PD patient-derived dopaminergic neurons.

Oligodendroglia vulnerability in the human dorsal striatum in Parkinson's disease

The paper uses snRNA-seq and spatial transcriptomics to study oligodendroglia in Parkinson's disease, identifying disease-specific subclasses and transcriptomic changes linked to myelin integrity and cell communication.

Emergent glutamate & dopamine dysfunction in VPS35(D620N) knock-in mice and rapid reversal by LRRK2 inhibition

This study shows that VPS35(D620N) mutation leads to increased glutamate and dopamine transmission in mice, which can be reversed by LRRK2 inhibition.

Abundant non-inclusion α-synuclein pathology in Lewy body-negative LRRK2-mutant cases

The paper shows that LRRK2-mutant cases without Lewy bodies have abundant non-inclusion α-synuclein pathology detected by PLA, unlike Lewy body disease cases.

Widespread Distribution of α-Synuclein Oligomers in LRRK2-related Parkinson's Disease

This study examines the distribution of α-synuclein oligomers in LRRK2-related Parkinson's disease, finding a negative correlation between oligomers and Lewy-related pathology.

LRP10 promotes trafficking of progranulin and prosaposin to lysosomes

This study identifies LRP10 as a regulator of progranulin and prosaposin lysosomal trafficking and microglia homeostasis, linking its dysfunction to neurodegenerative diseases.

Neuroimaging and plasma biomarker differences and commonalities in Lewy body dementia subtypes

The paper compares neuroimaging and plasma biomarkers in Lewy body dementia subtypes, finding differences in white matter integrity and plasma markers between dementia with Lewy bodies and Parkinson's disease dementia.

Increased burden of rare risk variants across gene expression networks predisposes to sporadic Parkinson's disease

The paper identifies genes regulating alpha-synuclein homeostasis and shows their differential expression correlates with increased rare risk variant burden in Parkinson's disease.

Identification of immune-mitophagy related gene in PD based on single-cell sequencing and Mendelian randomization

The paper identifies four genes linking mitophagy and immune responses in Parkinson's disease using single-cell sequencing and Mendelian randomization.

The Role of Alpha Synuclein in Synucleinopathy: Impact on Lipid Regulation at Mitochondria ER Membranes

This paper investigates the role of alpha-synuclein in lipid regulation at MAM domains in synucleinopathies, showing disease-specific lipid alterations and Syn's impact on phosphatidylserine metabolism.

Investigating shared genetic architecture between pigmentation genetics and Parkinson's Disease

The paper examines genetic links between pigmentation traits and Parkinson's Disease using LDSC, PRS, MR, and multi-trait analysis, finding limited shared variation and no causal relationships.