Parkinson's Disease Mechanisms and Treatments

The paper investigates associations between gut microbiome composition and risk/prodromal markers of Parkinson's disease in elderly participants.

The paper shows that combining a Parkinson's disease mutation in synaptojanin 1 with Sac2 knockout in mice leads to severe neurological defects, suggesting Sac2 as a PD risk gene.

The paper identifies LRRK2 as a regulator of clathrin-mediated endocytosis and links clathrin-trafficking pathways to Parkinson's disease risk.

This study shows that developmental dieldrin exposure increases male-specific motor deficits and dopamine handling issues in a synucleinopathy model, without affecting nigral neuron loss.

The paper uses machine learning to identify neurodegeneration signatures in non-human primates caused by patient-derived α-synuclein structures, showing that small aggregates are as toxic as larger fibrils.

This study shows that intra-mitochondrial proteostasis influences alpha-synuclein and Aβ42 aggregation, while mitochondrial stress factors like complex I inhibition do not affect these pathologies.

This paper introduces a pharmacodynamic fMRI method to quantify Parkinson disease severity by measuring dopamine buffering capacity through levodopa response timing.

This study shows that LRRK2-G2019S mutation alters behavioral and synaptic responses to acute social stress in mice, suggesting impaired adaptive plasticity in neural circuits linked to psychopathology.

This study shows Rab27b regulates alpha-synuclein release, autophagic clearance, and toxicity, linking it to synucleinopathy pathogenesis.

This study identifies cell types associated with brain complex traits using GWAS and single-cell transcriptomics, revealing novel roles for oligodendrocytes in Parkinson's disease.

The paper uses an in vivo electroretinogram screen in Drosophila to identify Rab10 as a strong LRRK2-G2019S substrate in dopaminergic neurons, distinguishing it from Rab3.

This study shows that common gene expression signatures in Parkinson’s disease are driven by changes in cell composition rather than true biological changes.

This study shows that Hsp27 reduces glycation-induced toxicity and aggregation of α-synuclein in cellular models.

This study uses continuous response force measurements to assess inhibitory control in Parkinson's disease patients, finding no deficits in response inhibition.

This study evaluates the role of PINK1 variants in Parkinson's disease risk using large datasets and finds no evidence supporting heterozygous PINK1 mutations as a risk factor.

The paper identifies transcriptomic signatures of brain regional vulnerability to Parkinson’s disease by analyzing gene expression patterns across Braak Lewy body stages in human brain datasets.

The paper investigates the genetic association between alcohol dehydrogenase genes and Parkinson’s disease risk using GWAS data and finds no significant association.

This study develops a neuronal model of Lewy body formation and shows that the process of Lewy body maturation, not just fibrillization, drives neurodegeneration in synucleinopathies.

The paper assesses pS935 LRRK2 levels in PBMCs of iPD and G2019S LRRK2 carriers, finding reduced levels in G2019S carriers with PD compared to those without PD or iPD.

This study identifies SNCA risk variants specific to RBD and overt synucleinopathies, finding distinct associations and opposite effects at the 3' end of SNCA.

This study shows that a polygenic risk score increases the likelihood of Parkinson's disease in LRRK2 p.G2019S carriers, with stronger effects in younger individuals.

This study shows that alpha-synuclein oligomers reduce mitochondrial SIRT3 activity, impair mitochondrial dynamics, and that AICAR treatment restores SIRT3 and improves mitochondrial dysfunction in Parkinson's disease models.

This paper introduces a centrifugation-based filtration protocol to isolate and quantify α-synuclein monomers, oligomers, and fibrils to improve experimental reproducibility in Parkinson's research.

The paper investigates the role of VPS13C variants in late-onset Parkinson disease, finding no significant association with rare variants but a nominal association with a haplotype.

This study examines how parkin deficiency affects cortico-basal ganglia circuit dynamics in mice, revealing altered interneuronal activity and oscillatory patterns linked to Parkinson's disease.

The paper investigates how alpha synuclein aggresomes impair centrosome functions, including microtubule organization and ciliogenesis, potentially contributing to Parkinson's disease pathology.

The paper investigates how nicotine protects dopaminergic neurons in C. elegans by activating mitochondrial stress pathways involving PINK-1 and D3 receptors.

This paper shows that excess α-synuclein impairs synaptic vesicle recycling by sequestering Hsc70, and that increasing Hsc70 levels can reverse this defect in a vertebrate synapse.

The paper examines the relationship between grey and white matter pathology and cognitive/motor deficits in Parkinson's disease using MRI data and clinical scores.

The paper shows misfolded α-synuclein, generated via PMCA, binds cardiolipin and causes hyperactive mitochondrial respiration in neuroblastoma cells without functional deficits.