Parkinson's Disease Mechanisms and Treatments

This study identifies Snca as a genetic modifier of Atp7a in female mice, revealing a potential role for Snca in the ER-Golgi system in a sex-dependent manner.

This study compares polygenic risk scores for Parkinson's disease across seven ancestries, finding varying predictive accuracy and highlighting the need for ancestry-specific models.

This study shows that patient-derived microglia in midbrain organoids induce endogenous alpha-synuclein pathology without exogenous seeding.

The paper shows that LRRK2 kinase inhibitor treatment restores cilia, Hedgehog signaling, neuroprotective factors, and dopamine processes in Parkinson's linked-LRRK2 mutant mice striatum.

The paper examines how cholinergic signaling adapts in response to dopamine loss in Parkinson’s disease, finding that M4 receptor function declines regionally and temporally with dopaminergic degeneration.

This study investigates cortical network disruptions in Parkinson's disease using a mouse model, finding PV interneuron dysfunction drives maladaptive plasticity and motor deficits.

The paper uses structural and chemical biology methods to show EX-6 binds selectively to α-synuclein fibrils in MSA tissue, with a 10-fold preference over PD tissue.

The paper identifies a neural mechanism in dopamine-deficient zebrafish linking stress-induced sensory processing to motor control through hyperactive brain regions.

This paper develops a global kinetic model of lipid-induced alpha-synuclein aggregation and identifies how squalamine inhibits this process by reducing lipid-dependent primary nucleation.

This study shows copper supplementation reduces SOD1 misfolding and protects dopamine neurons in a mouse model of Parkinson's disease.

The paper identifies three rare coding variants in LRRK2 that disrupt GTP binding and kinase activity, supporting their role in Parkinson's disease risk and drug target potential.

This study compares dopamine and cortical neurons with PD mutations to identify cellular dysfunctions linked to different pathological phenotypes.

The paper compares two rat synucleinopathy models using multi-omics data to identify disease mechanisms and drug targets relevant to Parkinson's disease.

This study identifies a shared genetic architecture between Parkinson's disease and sleep-related traits, implicating the MAPT locus in both conditions through common biological pathways.

This study shows that pathological α-synuclein can cause granulovacuolar degeneration independently of tau, using a mouse model of α-synucleinopathy.

This study demonstrates that SNCA-targeted epigenome therapy reduces α-synuclein expression, aggregation, and motor deficits in a PD mouse model.

The paper identifies a Lewy-MSA hybrid fold of α-synuclein in atypical MSA, linking distinct filament structures to neuronal versus oligodendroglial pathologies.

This study shows that increasing SLP-2 levels reduces alpha-synuclein-induced mitochondrial damage and neurodegeneration in Parkinson's disease models.

This study uses Mendelian randomization to find coffee consumption is causally linked to later age-at-onset of Parkinson's disease but not to disease risk or progression.

The paper develops a CRISPR-CAS9 platform with machine learning to study PINK1-mitophagy in Parkinson's disease using iPSC-derived neurons, identifying key genes and validating their roles.

This study uses multiplex proteomics to identify CSF biomarkers of clinical and neuropathological heterogeneity in Lewy body dementia.

The paper uses CRISPR screens to identify OXR1 and EMC4 as modifiers of α-synuclein aggregation in Parkinson's disease and related synucleinopathies.

Hybrid type-II inhibitors RN277 and RN341 target inactive LRRK2 with far fewer kinase off-targets than Rebastinib, preserve S935 phosphorylation, and rescue kinesin motility in vitro.

This paper introduces UltraID-LIPA, a platform combining optogenetic-induced protein aggregation and proximity biotinylation to identify α-synuclein-interacting proteins, revealing endolysosomal proteins' role in early aggregation.

This study shows that Lrrk2 and Snca gene variants do not affect encephalitis severity in newborn mice infected with reovirus T3D via direct brain inoculation, unlike intranasal infection.

The paper identifies Anxa1 as a marker for PD-vulnerable dopamine neurons and shows they respond oppositely to excitatory inputs compared to resilient Vglut2+ neurons.

The paper identifies SNX5 knockdown as protective against alpha-synuclein toxicity in a Parkinson's disease cell model through genome-wide RNA interference screening.

The paper identifies presynaptic and postsynaptic risk genes and key connectomes involved in pathological α-synuclein spreading using mathematical models and gene regulatory network analysis.

This study examines how genetic variants in Saccharomyces cerevisiae affect paraquat toxicity, finding strain-specific differences in growth, oxidative stress, and vacuolar responses.

This study uses fluorescence lifetime imaging to track alpha-synuclein aggregation in neurons, revealing that seeds disassemble before escaping endolysosomes and triggering cytosolic aggregation.