Parkinson's Disease Mechanisms and Treatments

The paper identifies two unexploited genes related to oxidative stress in Parkinson's disease using a pipeline to address missing data in disease-associated gene databases.

This study uses whole-genome sequencing to identify new genetic loci and structural variants associated with progressive supranuclear palsy, including novel signals in APOE and H1/H2 haplotype region variants.

The paper identifies transcriptomic changes in oligodendrocytes and precursor cells linked to Parkinson's disease outcomes and shows their predictive value for cognitive and depressive symptoms.

This study identifies residues 2-7 of alpha-synuclein as regulators of amyloid formation, showing they slow fibril formation and reduce aggregation in vitro and in vivo without affecting membrane binding.

This study compares alpha-synuclein aggregation under conditions that promote or negate liquid-liquid phase separation, showing that phase separation leads to more structurally variable and toxic fibrils.

The paper identifies a novel signalling circuit involving TRPM2, NOX2, Ca2+, Zn2+, and complex III that drives cytotoxic ROS production in Parkinson's disease.

This study identifies distinct presynaptic protein networks in Lewy body dementia that differ from Alzheimer's disease using network proteomics.

This study investigates the genetic role of the NLRP3-inflammasome in Parkinson's disease using polygenic risk scores and Mendelian randomization, finding no significant associations.

The paper shows that loss of primary cilia in specific striatal cell types reduces dopaminergic neuroprotection in Parkinson's disease, linked to impaired Hedgehog signaling.

This paper investigates the therapeutic potential of beta2-adrenergic agonists, particularly levalbuterol, in Parkinsonism and other disorders by examining their anti-inflammatory and anti-tumor effects.

This study examines how O-GlcNAcylation at T72 and S87 of α-synuclein affects its monomer dynamics and aggregation kinetics, revealing differential impacts on protein behavior.

This paper combines two global monogenic Parkinson's disease initiatives to create a comprehensive cohort and infrastructure for studying multi-ancestry genetic factors and disease expression.

This paper develops an iPSC platform to rapidly generate alpha-synuclein inclusions and investigates their formation, subtypes, and molecular interactions.

This study shows that deleting ATP13A2 in adult mice leads to progressive dopaminergic degeneration and lysosomal issues, mimicking human neurodegenerative diseases.

The paper compares DNA methylation patterns in white matter of MSA, PD, and PSP to identify shared and disease-specific alterations.

This study shows that the Bri2 BRICHOS domain inhibits α-synuclein oligomer formation and toxicity by suppressing secondary nucleation and binding oligomers, suggesting its potential as a therapeutic target for Parkinson's disease.

This study investigates how salt concentration affects the phase separation and aggregation of alpha-synuclein, revealing distinct salt dependencies and dynamic transitions between assembly states.

This study shows that the LRRK2-G2019S mutation alters AMPAR trafficking and composition in striatal projection neurons, specifically affecting GluA1 subunits and impairing synaptic plasticity.

This study investigates how α-synuclein aggregates in the basolateral amygdala affect synaptic structure and function in a mouse model of Parkinson's disease.

This study evaluates the neuroprotective effects of PT150, a glucocorticoid receptor modulator, in a rotenone-induced Parkinson's disease mouse model, showing reduced dopaminergic neuron loss and α-synuclein accumulation.

The paper examines changes in serotonergic and dopaminergic neurons in the dorsal raphe nucleus of a Parkinson's disease mouse model following 6-OHDA injection.

This study shows moderate intensity aerobic exercise improves motor deficits and reduces blood biomarkers in a Parkinson's rat model without increasing striatal dopamine or tyrosine hydroxylase.

This study shows that Parkinson's disease patients exert less grip force for low incentives, linking reduced motor effort to putaminal dopamine loss.

The paper examines how polygenic scores and lifestyle factors influence age at onset in Parkinson's disease, finding that lifestyle factors have a larger impact than genetic variants.

This paper develops an adaptive wheel exercise system for mice with Parkinson's disease to enable non-aversive, performance-tracked exercise and neurophysiological measurement.

The paper models disease progression in Lewy body disorders using neuropathological data, identifying three distinct trajectories of alpha-synuclein pathology with different clinical associations.

The paper investigates the effects of the Parkin R274W mutation on muscle physiology through the PARIS-PGC-1α pathway in mice.

This study develops a high-affinity DARPin that binds to LRRK2's WD40 domain, improving structural analysis and revealing its role in disrupting LRRK2 filaments and Rab8A phosphorylation.

The paper measures LRRK2 kinase activity via pT73-Rab10 in serum, linking it to inflammation and Parkinson's disease severity.

This study shows that LRRK1 and LRRK2 are essential for dopaminergic neuron survival, as their deletion leads to age-dependent neurodegeneration in mice.