Parkinson's Disease Mechanisms and Treatments

The paper shows that inhibiting LRRK2 kinase activity rescues dopamine deficits in VPS35 p.D620N knock-in mice by normalizing DAT function and reducing hyperlocomotion.

This study investigates the role of LRP10 in Lewy body diseases, showing it regulates α-synuclein levels and interacts with a disease-associated variant.

The paper investigates strain-specific susceptibility to MPTP in mice, finding differences in apoptotic factors and mitochondrial complexes that influence neuroprotection.

This study demonstrates that BH4 deficiency exacerbates PD-related stressors and that BH4 augmentation protects dopaminergic neurons in multiple models.

This study attempts to reproduce and replicate a machine learning model for predicting Parkinson's disease progression using MRI data, finding lower performance than the original study.

The paper examines the association between clonal hematopoiesis and Parkinson's disease using whole exome sequencing data from controls and patients.

The paper investigates how mutations in the PINK1 kinase domain affect its interaction with the Parkin Ubl domain using molecular docking and dynamics simulations.

This study identifies a new susceptibility locus, PLA2G4C, for Multiple System Atrophy through a genome-wide association study and functional analysis of a risk variant.

The paper investigates how GTPase and kinase domain mutations in LRRK2 affect endosomal localization and Rab phosphorylation, finding that GTPase-inactivating mutants lead to more LRRK2+ endosomes and higher Rab phosphorylation.

The paper shows that LRRK2 mutations disrupt autophagosome transport in neurons by creating a tug-of-war between dynein and kinesin motors, contributing to Parkinson's disease pathogenesis.

This study shows that synthetic neuromelanin induces inflammation and may contribute to dopaminergic neuron degeneration in a new mouse model of Parkinson's disease.

The paper investigates mitochondrial dysfunction in iPSC-derived dopaminergic neurons from idiopathic Parkinson's disease patients, finding reduced mitochondrial fitness and ATP availability linked to decreased neuronal excitability.

This study shows that Rit2 loss in dopamine neurons causes PD-like symptoms in mice, with sex-specific differences in disease progression and response to treatment.

This study shows octopamine reprograms astrocytes to protect neurons from α-synuclein toxicity through metabolic pathways.

Peripheral blood-derived cells can be employed to stratify Parkinson's disease patients most likely to respond to LRRK2-related therapeutics.

This study examines electrophysiological and gene expression changes in dopaminergic neurons from Parkinson's disease patients and those with GBA1 mutations, identifying synaptic dysfunction and ECM pathway dysregulation.

This study shows that the LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance by hyperphosphorylating ERM proteins, which disrupts the Ezrin/Atg7 interaction and autophagy.

This study investigates the genetic and genomic links between NBIA and PD, finding no strong association and suggesting they may be distinct conditions.

This study identifies β-neurexins as presynaptic proteins that bind to α-synuclein preformed fibrils, impairing presynaptic organization and contributing to synucleinopathy pathology.

This study investigates how manganese exposure increases microglial LRRK2 activity, leading to neuroinflammation and toxicity, with exacerbation in LRRK2 G2019S mutation.

The paper identifies PSER129 accumulation in healthy olfactory bulb mitral cells and links it to synucleinopathy pathogenesis through protein interactome analysis.

This study shows that nitration of alpha-synuclein after fibrillization reduces its seeding activity and pathology formation in neurons and in vivo.

The paper identifies vulnerable DA neuron subpopulations in Drosophila PD models using split-GAL4 and highlights an age-related caveat of the system.

This paper compares transcriptomic profiles in En1-hemizygous mice to identify gene expression differences linked to susceptibility to Parkinson's-like neurodegeneration.

The paper identifies molecular signatures of neuronal vulnerability to α-synuclein and tau toxicity, showing differential susceptibility independent of expression levels.

This study shows that tyrosinase-induced neuromelanin accumulation in mouse locus coeruleus neurons causes hyperactivity, transcriptional changes, and degeneration, mimicking early stages of Alzheimer's and Parkinson's disease.

The paper identifies metabolic alterations in Parkinson's disease using human brain transcriptomes and experimental models, finding regional correlations and heterogeneity in metabolic pathways.

This study identifies volatile compounds in sebum that differentiate Parkinson's Disease and REM sleep behaviour disorder, showing changes over disease progression.

This study shows that auxilin deficiency causes Parkinson's disease by disrupting dopamine transporter function and synaptic vesicle sorting, leading to dopamine homeostasis disruption and neurodegeneration.