Parkinson's Disease Mechanisms and Treatments

Dopamine 2 receptor ablation from cholinergic neurons attenuates L-DOPA induced dyskinesias.

This study shows that removing dopamine 2 receptors from cholinergic neurons reduces L-DOPA-induced dyskinesias while maintaining its therapeutic benefits.

Knockout of Rab27b exacerbates neuropathology in alpha-synuclein mouse models

This study shows that Rab27b knockout worsens alpha-synuclein pathology in mouse models of Parkinson's disease.

Adaptation of α-synuclein fibrils following multiple system atrophy transmission to mice

This study reports atomic resolution cryo-EM structures of α-synuclein fibrils from an MSA patient before and after transmission to a transgenic mouse model, showing structural adaptations while maintaining key features.

Modeling interregional propagation of α-synuclein in human striatal-midbrain assembloids

This study uses human striatal-midbrain assembloids to show that α-synuclein pathology spreads from the striatum to midbrain dopaminergic neurons, causing functional impairment.

Aberrant CD4+ T cell refeeding response impairs neuro-immune crosstalk in Parkinson's disease

The paper shows that PD patients have altered CD4+ T cell responses to fasting/refeeding, leading to impaired neuro-immune signaling through a dysfunctional metabolic program in neurons.

Sex-Dependent Effects of Glutamatergic Disruption on Dopaminergic Neuron Subtype Vulnerable in Parkinson's Disease

This study shows that disrupting NMDA receptor-mediated glutamatergic input to ALDH1A1+ dopaminergic neurons causes sex-specific feeding abnormalities linked to Parkinson's disease.

An isogenic single-cell atlas of familial Parkinson's disease mutations reveals convergent changes in dopamine neurons

This study creates an isogenic single-cell atlas of familial Parkinson's disease mutations, revealing shared transcriptional changes in dopamine neurons across diverse genetic backgrounds.

Exercise Evokes Retained Motor Performance without Neuroprotection in a Mouse Model of Parkinson's Disease

The paper investigates the effects of exercise on motor performance and neurophysiology in a Parkinson's disease mouse model, finding no neuroprotection but identifying exercise-induced excitatory changes in the substantia nigra.

Systematic screening identifies elevated neurovascular BCL-XL in Parkinson's disease.

The paper identifies BCL-XL as a potential regulator of the neurovascular unit in Parkinson's disease through systematic screening of -Synuclein strain responses in pericytes.

A high-content imaging workflow to screen for molecules that reduce cellular uptake of α-synuclein preformed fibrils

The paper describes a high-content imaging assay to screen small molecules that reduce cellular uptake of α-synuclein preformed fibrils in hiPSC-derived cells, identifying compounds that effectively lower intracellular PFF load.

Nanoscale CaV channel reorganization links alpha-synuclein pathology to calcium-dependent transcriptional dysregulation

This study shows that alpha-synuclein fibrils reorganize CaV channels, increasing their clustering and causing calcium-dependent transcriptional dysregulation in neurons.

Multiscale brain-wide mapping of α-synuclein-driven dopaminergic degeneration and white matter impairment in α-synucleinopathy mice

This paper maps α-synuclein pathology and dopaminergic degeneration in mice using multimodal imaging and microscopy, showing spread along the nigrostriatal pathway and microstructural changes.

Ancestry-specific immune signatures in Parkinson's disease: a rare variant burden analysis in Montreal and Guadeloupe cohorts

This study identifies ancestry-specific immune signatures in Parkinson's disease through rare variant analysis in Montreal and Guadeloupe cohorts, revealing divergent molecular pathways associated with disease.

Cell- and state-specific plasticity of striatal glutamatergic synapses is critical to the expression of levodopa-induced dyskinesia

This study identifies GluN2B-containing NMDAR up-regulation in iSPNs as a key mechanism in LID, showing that targeting these receptors can reduce dyskinesia without affecting levodopa's motor benefits.

Kir4.2 deficiency drives progressive Parkinson's disease-like motor, cognitive and neuropathological phenotypes in mice

This study shows that Kir4.2 deficiency in mice causes PD-like motor, cognitive, and neuropathological symptoms, establishing a new model for PD research.

Cell vulnerability within the sublaterodorsal tegmental nucleus underlies REM sleep behaviour disorder in prodromal α-synucleinopathy

The paper shows that synucleinopathy in SLD glutamatergic neurons causes RBD and Parkinson's-like deficits in mice.

A Versatile AAV-TH-SNCA Model to Study Early α-Synuclein Pathology and Intervention

This paper develops an optimized AAV.TH.SNCA model to study early α-synuclein pathology in mice, showing that motor deficits and neurochemical changes occur before neuronal loss.

Single cell eQTL mapping reveals convergent glial-neuronal risk architecture in Parkinson's disease

The paper fine-maps PD GWAS signals across cell types, revealing convergent glial-neuronal risk genes and a shared vesiculopathy network.

Sensorimotor basal ganglia circuit asymmetry explains lateralized motor dysfunction in early Parkinson's disease

This study identifies subregional basal ganglia pathology in early Parkinson's disease using MRI, showing associations with motor symptom lateralization and demonstrating the potential of anatomically guided spatial analysis for circuit-level biomarkers.

Genetically encoded nAChR upregulation is neuroprotective in female parkinsonian mice

This study shows that upregulation of β2* nAChRs in SNc DA neurons protects female parkinsonian mice from neurodegeneration without ligand activation.

Motor sequence analysis as a sensitive biomarker of dopaminergic degeneration in a non-human primate model of parkinsonism

This study shows that motor sequence analysis is more sensitive than traditional metrics in detecting early dopaminergic dysfunction in a primate model of parkinsonism.

Cell type-selective AADC expression reduces motor deficits and dyskinesia in Parkinson's disease mouse models

This study shows that cell type-specific AADC expression in Parkinson's disease models reduces motor deficits and dyskinesia more effectively than broad targeting.

Lysosome-acidifying nanoparticles rescue A30P α-synuclein induced neuronal death in cellular and Drosophila models of Parkinson's disease

This study shows lysosome-acidifying nanoparticles rescue neuronal death in A30P α-synuclein models by restoring lysosomal function and autophagy.

STIP1/HOP Promotes the Formation of Cytotoxic α-Synuclein Oligomers

This study identifies how STIP1/HOP interacts with a-Syn to promote toxic oligomer formation in synucleinopathies.

Mutational Scanning of α-Synuclein using a Clickable Protein Tag Reveals Determinants of Membrane-Induced Aggregation

The paper uses clickable protein tags to study α-synuclein aggregation in yeast, revealing membrane interactions drive aggregation and identifying key residues that influence this process.

α-Synuclein Facilitates Spontaneous Dopamine Release in a Calcium- and Phosphorylation-Dependent Manner

This study shows α-synuclein modulates spontaneous dopamine release via calcium and phosphorylation-dependent mechanisms, independent of full-fusion recycling.

Genome-wide association study of copy number variations in Parkinson's disease

This study conducts a genome-wide association study of copy number variations in Parkinson's disease, identifying a significant PRKN deletion but limited replication in an independent dataset.

Genetic and Proteomic Investigation of the Smoking-Parkinson Disease Association

This study investigates the causal relationship between smoking and Parkinson's disease using genetic and proteomic data, identifying shared biological pathways and potential therapeutic targets.

Full-Length Molecular Models of Brain-Derived α-Synuclein Fibrils Reveal a Fuzzy-Coat-Mediated Mechanism for Selective Peptide Binding

The Global Parkinson's Disease Genetics (GP2) Genome Browser

The paper introduces a genome browser for Parkinson's disease genomic data, integrating WGS and CES samples with variant annotations and ancestry stratification.