Parkinson's Disease Mechanisms and Treatments

Lack of genetic evidence for NLRP3-inflammasome involvement in Parkinson's disease pathogenesis

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.

Tet2 loss suppress α-synuclein pathology by stimulating ciliogenesis

The paper identifies that Tet2 loss promotes ciliogenesis and reduces α-synuclein pathology in Parkinson's disease models.

Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinsons disease

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.

Imaging spatial transcriptomics reveals molecular patterns of vulnerability to pathology in a transgenic α-synucleinopathy model

The paper uses imaging spatial transcriptomics to identify neuronal subtypes vulnerable to -synuclein pathology in a transgenic mouse model and finds Plk2 and hSNCA expression are key to pathology development.

Post-translational Modification of α-Synuclein Modifies Monomer Dynamics and Aggregation Kinetics

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.

Understanding monogenic Parkinson's disease at a global scale

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.

Rapid iPSC inclusionopathy models shed light on formation, consequence and molecular subtype of alpha-synuclein inclusions

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

Templating of Monomeric Alpha-Synuclein Induces Inflammation and SNpc Dopamine Neuron Death in a Genetic Mouse Model of Synucleinopathy.

This study shows that monomeric alpha-synuclein induces inflammation and dopamine neuron death in A53T SNCA mice, suggesting a mechanism for PD in humans with SNCA mutations.

Single-nucleus and spatial transcriptomic analysis identified molecular features of neuronal heterogeneity and distinct glial responses in Parkinson's disease.

This study uses single-nucleus and spatial transcriptomics to identify neuronal heterogeneity and glial responses in Korean Parkinson's disease patients.

Neurotoxic Methamphetamine Doses Alter CDCel-1 Levels and Its Interaction with Vesicular Monoamine Transporter-2 in Rat Striatum

This study shows binge METH alters CDCel-1 levels and its interaction with VMAT2 in rat striatum, with individual differences in response to METH neurotoxicity.

Adult-Onset Deletion of ATP13A2 in Mice Induces Progressive Nigrostriatal Pathway Dopaminergic Degeneration and Lysosomal Abnormalities

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

Loss of PINK1 causes age-dependent mitochondrial trafficking deficits in nigrostriatal dopaminergic neurons through aberrant activation of p38 MAPK

This study shows that PINK1 loss causes age-dependent mitochondrial trafficking deficits in dopaminergic neurons via p38 MAPK hyperactivation, leading to impaired mitochondrial motility and increased oxidative stress.

Pathogenic LRRK2 causes age-dependent and region-specific deficits in ciliation, innervation and viability of cholinergic neurons

This study shows that pathogenic LRRK2 mutations cause age-dependent and region-specific deficits in ciliation, innervation, and viability of cholinergic neurons in mice.

DNA methylation patterns in the frontal lobe white matter of multiple system atrophy, Parkinson's disease, and progressive supranuclear palsy: A cross-comparative investigation

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

Characterization of Dnajc12 knockout mice, a model of hypodopaminergia

This study characterizes Dnajc12 knockout mice, showing reduced dopamine and serotonin levels, altered behavior, and potential therapeutic implications for biogenic amine disorders.

Parkinson's-linked LRRK2-G2019S derails AMPAR trafficking, mobility and composition in striatum with cell-type and subunit specificity

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.

Cortico-amygdala synaptic structural abnormalities produced by templated aggregation of α-synuclein

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

Gene expression asymmetry in Parkinson's Disease; variation of CCT and BEX gene expression levels are correlated with hemisphere specific severity

The paper examines gene expression asymmetry in Parkinson's Disease, finding that CCT and BEX gene expression levels vary between hemispheres and correlate with symptom onset side.

Neuroprotective efficacy of the glucocorticoid receptor modulator PT150 in the rotenone mouse model of Parkinsons 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.

Serotonergic and dopaminergic neurons in the dorsal raphe are differentially altered in a mouse model for parkinsonism.

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.

PINK1-G411S mutant increases kinase stability and enhances mitochondrial-linked functions

This study investigates how the PINK1-G411S mutant affects PINK1 function, showing increased kinase stability and mitochondrial-linked functions through molecular dynamics analysis.

Moderate intensity aerobic exercise in 6-OHDA-lesioned rats alleviates established motor deficits and reduces neurofilament light and glial fibrillary acidic protein serum levels without increased striatal dopamine or tyrosine hydroxylase protein

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.

Putaminal dopamine modulates movement motivation in Parkinson's disease

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

The combined effect of lifestyle factors and polygenic scores on age at onset in Parkinson's disease

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.

Adaptive Wheel Exercise for Mouse Models of Parkinson's Disease

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

A Novel Susceptibility Locus in NFASC Highlights Oligodendrocytes and Myelination in Progressive Supranuclear Palsy Pathology

The paper performs a GWAS on PSP in the Iberian population, replicates known risk variants, and identifies a novel locus in NFASC/CNTN2 associated with oligodendrocyte and myelination processes.

Cortical synaptic vulnerabilities revealed in a α-synuclein aggregation model of Parkinson's disease

This study identifies excitatory synapses as primary targets of α-synuclein aggregation in a Parkinson's disease mouse model, revealing spatial and temporal patterns of synaptic vulnerability.

α-Synuclein acts as a cholesteryl-ester sensor on lipid droplets regulating organelle size and abundance.

This study shows α-Synuclein binds lipid droplets, senses cholesteryl-ester, regulates organelle size and abundance, and links its dysfunction to neurodegenerative diseases.

Transcriptional pathobiology and multi-omics predictors for Parkinson's disease

This study identifies 1,111 PD-associated RNAs in blood and develops a multi-omics model with AUC 0.89 for PD diagnosis, offering insights into pathobiology and potential clinical applications.

15-Lipoxygenase-Mediated Lipid Peroxidation Regulates LRRK2 Kinase Activity

This study identifies 15-lipoxygenase-mediated lipid peroxidation as a regulator of LRRK2 kinase activity, linking it to Parkinson's disease pathogenesis.