Parkinson's Disease Mechanisms and Treatments

Dopamine release from Parkinson's patient-derived neurons is disrupted due to impaired synaptic vesicle loading

The paper investigates dopamine release defects in Parkinson's patient-derived neurons and identifies reduced VMAT2 function as the cause.

Lipid Acyl Chain-Driven α-Synuclein Fibril Polymorphisms and Neuronal Pathologies

This study shows that age-related membrane changes affect α-synuclein fibril structure and pathogenicity, linking membrane dynamics to neurodegeneration.

Integrated Gait and Pose Analysis Utilizing Computer Vision for Parkinsonian Behavioral Phenotyping in Mice

The paper develops a combined gait and pose analysis method using CatWalk XT videos to detect motor phenotypes in mice with synucleinopathy.

Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies

This study identifies structural and functional differences in alpha-synuclein fibrils from Parkinson's disease, Dementia with Lewy Bodies, and Multiple System Atrophy, linking these differences to disease-specific cellular responses and potential therapeutic targets.

Gut-Initiated Alpha Synuclein Fibrils Drive Parkinson's Disease Phenotypes: Temporal Mapping of non-Motor Symptoms and REM Sleep Behavior Disorder

This study shows that gut-to-brain propagation of alpha-synuclein fibrils induces REM sleep behavior disorder and other non-motor and motor Parkinson's disease phenotypes.

Discovery and characterization of UCB-1A: the first PET radioligand for imaging synaptic vesicle glycoprotein 2C

This paper develops UCB-1A, the first PET radioligand for imaging SV2C, showing it binds selectively to SV2C in brain regions and is suitable for Parkinson's disease studies.

Massive-scale single-nucleus multi-omics identifies novel rare noncoding drivers of Parkinson's disease

The paper identifies rare noncoding variants associated with Parkinson's disease using multi-omic data from over 3.3 million nuclei.

Faecalibacterium prausnitzii, depleted in the Parkinson's disease microbiome, improves motor deficits in α-synuclein overexpressing mice

Oral Faecalibacterium prausnitzii, the taxon most consistently depleted in PD stool, improved motor and GI deficits and lowered α-synuclein aggregates in male Thy1-ASO mice.

Study the dynamics of behavioral and biochemical parameters in the PARK2-knock-out mice model of Parkinson's disease

This study examines the behavioral and biochemical changes in PARK2-knockout mice to understand Parkinson's disease dynamics, finding age-related but not human-like PD manifestations.

Ultra-performance liquid chromatography-mass spectrometry analysis of post-mortem brain tissue reveals specific amino acid profile dysregulation in Parkinson's Disease and Alzheimer's Disease patients

This study uses UPLC-MS to analyze amino acid profiles in post-mortem brain tissue from PD and AD patients, revealing region-specific metabolic changes.

Reactive Astrocytes Drive Extracellular Acidification to Mediate α-Synuclein Neurodegeneration

This study identifies a mechanism by which reactive astrocytes drive neurodegeneration in synucleinopathies through extracellular acidification and neuronal ASIC1a activation.

Fluorescent Peptide-based Probe for the Detection of Alpha-synuclein Aggregates in the Gut

This paper develops a peptide-based fluorescent probe to detect alpha-synuclein aggregates in the gut, showing high accuracy and specificity for early Parkinson's disease diagnosis.

Parkinson's disease linked LRRK2 G2019S drives oxidative nuclear DNA damage and PARP1 hyperactive signaling

This study shows that the LRRK2 G2019S mutation causes oxidative nuclear DNA damage and PARP1 hyperactivation, leading to cellular vulnerability in Parkinson's disease.

PRMT1/Hmt1 drives α-synuclein aggregate dissolution through a catalysis-independent pathway

This study shows PRMT1/Hmt1 reduces α-synuclein aggregates and toxicity without requiring their methyltransferase activity, revealing a new pathway for protein quality control.

Shift in motor-state equilibrium explains gait therapy effects of apomorphine in experimental Parkinsonism

This study investigates how apomorphine affects gait in a Parkinson's disease rat model, finding it improves walking distance but reduces limb velocity, with changes in cortical gamma rhythms influencing motor state transitions.

Stochastic Misfolding Drives the Emergence of Distinct α-Synuclein Strains

This study shows that stochastic misfolding leads to the formation of distinct α-synuclein strains both in vitro and in vivo, resulting in different disease phenotypes.

Cytosolic interaction with RNA-helicase DDX39A titrates viral RNA G-quadruplex mediated α-Synuclein amyloidogenesis

The paper shows that DDX39A interaction with RNA reduces α-Synuclein amyloid formation, while viral rG4s enhance it, linking RNA dynamics to Parkinson's disease pathogenesis.

A Degron Decoy System Co-opts Pathological Seeding to Enable Clearance of Multimeric α-Synuclein.

This paper introduces a degron decoy system that uses pathological seeding to clear multimeric α-synuclein by co-aggregating with oligomers and enabling degradation via a small molecule trigger.

Alpha-synuclein overexpression triggers divergent cellular responses and post-translational modifications in SH-SY5Y and ReNcell VM models

This study shows that alpha-synuclein overexpression causes different cellular responses and post-translational modifications in two neuronal cell models, highlighting context-dependent vulnerability in Parkinson's disease.

Detection of alpha synuclein seeding activity in tear fluid in patients with Parkinson's disease

This study detects alpha-synuclein seeding activity in tear fluid from Parkinson's disease patients using aSynSAA, showing higher activity in PD compared to controls and prion disease.

SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids

This study shows that SNCA triplication in human midbrain organoids causes early proteostasis disruption and extracellular matrix changes before neurodegeneration.

Chronic nicotine reduces nigral dopaminergic activity and remodels pedunculopontine cholinergic subpopulations

This study examines how chronic nicotine affects dopaminergic neurons in the substantia nigra and cholinergic neurons in the pedunculopontine nucleus, revealing changes in their activity and morphology that may contribute to Parkinson's disease resilience.

Glucosylceramide induced ectosomes propagate pathogenic α-synuclein in Parkinson's disease

This study shows that glucosylceramide-induced ectosomes transmit pathogenic α-synuclein between neurons in Parkinson's disease.

Multimodal Neuroimaging Reveals Distinct Characteristics of Levodopa-Induced Dyskinesias in de novo Parkinsons Disease Patients

This study uses multimodal neuroimaging to identify morphological and functional differences in de novo Parkinson's disease patients with and without levodopa-induced dyskinesias.

Machine learning and burden analyses highlight novel candidate genes in Parkinson's disease

The paper integrates machine learning and rare variant burden analysis to identify novel candidate genes for Parkinson's disease.

Introducing PIGMO, a novel PIGmented MOuse model of Parkinson's disease

The paper introduces a novel mouse model of Parkinson's disease using a modified viral vector to induce pigmentation and pathological features associated with the disease.

VMAT2 dysfunction impairs vesicular dopamine uptake, driving its oxidation and α-synuclein pathology in DJ-1-linked Parkinson's disease neurons

This study shows that DJ-1 deficiency impairs VMAT2 function and vesicle dynamics, leading to dopamine oxidation and α-synuclein pathology in Parkinson's disease neurons.

Modeling the pathological brain-gut axis in Parkinson's disease using human iPSC derived brain-intestinal assembloids

This study uses human iPSC-derived brain-intestinal assembloids to show synuclein propagation from brainstem to enteric neurons and identifies NRXN1-NLGN2 signaling as a key mediator.

Comprehensive Variant Effect Map of Parkin-Mediated Mitophagy in Parkinson's Disease

This paper maps the functional effects of Parkin variants in mitophagy, distinguishing pathogenic from benign variants with high accuracy.

A Functional Genetic Atlas of Parkin Resolves Variants of Uncertain Significance and Predicts Parkinson's Disease Age at Onset

The paper functionally characterizes PRKN variants using a pooled assay, reclassifies variants of uncertain significance, and predicts Parkinson's disease age at onset.