Parkinson's Disease Mechanisms and Treatments

Integrative lipidomics of brain and plasma uncovers sex-specific metabolic signatures in Parkinson's disease

The paper identifies shared and sex-specific lipidomic changes in brain and plasma of Parkinson's disease models and patients, showing peripheral lipid signatures reflect CNS pathology.

Transition Metal Dichalcogenide Nanoflowers Rescue Immune Cells from the Cytotoxic Effects of Amyloid Aggregates

This study investigates the cytoprotective effects of TMD nanoflowers on immune cells exposed to α-synuclein fibrils, finding MoSe2 NFs more effective in mitigating toxicity than MoS2 NFs.

Mapping the comorbid landscape of Parkinson's disease and Crohn's disease along the gut-blood-brain axis

This study maps the comorbid landscape of Parkinson's disease and Crohn's disease through a multi-omics approach, revealing shared genetic and transcriptional mechanisms along the gut-blood-brain axis.

Large-scale visualisation of α-synuclein oligomers in Parkinson's disease brain tissue

This paper introduces ASA-PD, an imaging method to detect and map α-synuclein oligomers in Parkinson's disease brain tissue, revealing a specific subpopulation of nanoscale oligomers as an early hallmark of the disease.

p75NTR modulation by LM11A-31 counteracts oxidative stress and cholesterol dysmetabolism in a rotenone-induced cell model of Parkinson's disease

Polygenic risk scores and Parkinson's disease in South Africa: Moving towards ancestry-informed disease prediction

The paper evaluates polygenic risk scores for Parkinson's disease in a South African cohort, finding modest predictive performance and no ancestry-specific risk variants.

Neuroprotective Parkinson's Disease Therapeutic: Transition Metal Dichalcogenide Nanoflower Treatments Alleviate Pathological Cell Stress

This study shows that MoS2 and MoSe2 nanoflowers reduce alpha-synuclein toxicity in neurons and astrocytes, improve mitochondrial function, and extend lifespan in C. elegans.

Sex-specific microRNA regulators of Parkinson disease: insights from cohort-stratified simulations of compensatory pathway dynamics

This study uses Boolean modeling on PD cohorts to show sex-specific miRNA dysregulation affects mitochondrial biogenesis, mitophagy, and autophagy in Parkinson's disease.

In vivo validation of novel non-invasive PHP.eB AAVs as a potential therapeutic approach for alpha-Synucleinopathies

This study evaluates PHP.eB AAVs for reducing alpha-synuclein burden in a mouse model of alpha-synucleinopathies, showing reduced pathology and motor deficits.

Is synuclein aggregation a derived or ancestral trait? Ancestral sequence reconstruction uncovers stepwise evolution of synuclein aggregation

This study uses ancestral sequence reconstruction to show that synuclein aggregation evolved progressively, with fibril formation emerging in an ancestral node and being suppressed in beta-synuclein.

Identification of Small Molecule Dimethyoxyphenyl Piperazine Inhibitors of Alpha-Synuclein Fibril Growth

The paper identifies two dimethoxyphenyl piperazine analogs that inhibit alpha-synuclein fibril growth in vitro and from Lewy Body Disease brain tissue.

Genome-wide association study of REM sleep behavior disorder in Parkinson's disease

This study identifies genetic variants associated with REM sleep behavior disorder in Parkinson's disease and explores genetic correlations with neuropsychiatric traits.

NLX-112 is anti-inflammatory, upregulates GDNF and is neuroprotective against MPTP-induced nigrostriatal dopaminergic degeneration in mice

This study shows NLX-112 protects against MPTP-induced dopaminergic neuron loss in mice by reducing microgliosis, increasing GDNF, and improving locomotor activity.

Genetic modulation of mitochondrial NAD+ regeneration does not prevent dopaminergic neuron dysfunction caused by mitochondrial complex I impairment

This study shows that increasing mitochondrial NAD+ regeneration via MitoLbNOX does not rescue dopaminergic neuron dysfunction caused by complex I impairment in Parkinson's disease mice.

Infection and herbicide exposure implicate c-Abl kinase in α-Synuclein Ser129 phosphorylation

This study investigates how infection and pesticide exposure lead to α-Synuclein Ser129 phosphorylation through c-Abl kinase activation and identifies potential therapeutic targets.

Does COMT Play a Role in Parkinson's Disease Susceptibility Across Diverse Ancestral Populations?

This study investigates the association between COMT genetic variants and Parkinson's disease risk across diverse ancestries but finds no significant enrichment of COMT risk alleles in PD patients after multiple testing correction.

Restoration of locomotor function following stimulation of the A13 region in Parkinson's mouse models

This study shows that stimulating the A13 region in Parkinson's mouse models improves locomotor function and reduces bradykinesia by restoring motor function through neural remodeling.

A Dual Assay to Compare Protein Levels and Toxicity of Alpha-Synuclein Variants: Acute Expression of Wild-Type versus S129A

The paper develops an assay to compare protein levels and toxicity of alpha-synuclein variants, finding that the S129A mutant does not affect acute expression or toxicity.

Transmitted alpha-synuclein extracellular vesicles downregulate axonal flux of retrograde carriers in recipient neurons

This study shows that transmitted alpha-synuclein extracellular vesicles reduce retrograde axonal transport in recipient neurons, with effects dependent on endogenous alpha-synuclein interaction.

Secondary nucleation of α-Synuclein drives Mitochondria dysfunctions and Lewy body formation in Parkinson's Disease

This study identifies secondary nucleation of α-Synuclein as the key mechanism driving mitochondrial dysfunction and Lewy body formation in Parkinson's Disease.

Gabapentinoids promote striatal dopamine release and rescue multiple deficits of a mouse model of early Parkinson's

This study shows gabapentinoids enhance dopamine release in a Parkinson's mouse model and improve movement deficits by modulating calcium and GABAergic signaling.

Brain injury contributes to dopaminergic neurodegeneration, Lewy body pathology, and Parkinsonism preclinically with outcomes altered by T cell modulation

This study shows that mild brain injury increases dopaminergic neurodegeneration and Lewy body pathology in mice, and that reducing T cell infiltration improves outcomes.

Super-resolution microscopy of nanoscopic alpha-synuclein aggregates in brain samples indicates a subset of cells have disrupted protein homeostasis prior to Lewy body formation in Parkinson's disease

The paper uses super-resolution microscopy and SIMOA to analyze alpha-synuclein aggregates in Parkinson's disease brain samples and mouse models, finding larger aggregates in PD samples and differences based on extraction methods.

Downregulation of the Ca2+ sensor Synaptotagmin-1 (SYT1) in Parkinson's Disease: Insights from Gene Expression Profiling

The paper identifies differentially expressed genes in Parkinson's disease brain tissues, highlighting SYT1 as a significantly downregulated gene associated with calcium signaling and neurotransmitter release.

Glycated alpha-synuclein assemblies cause distinct Parkinsons disease pathogenesis in mice

This study shows that glycated alpha-synuclein assemblies cause distinct Parkinson's disease pathology in mice, including earlier onset of motor symptoms and increased neuroinflammation.

Leveraging structurally-informed bioorthogonal conjugation for alpha synuclein fibril surveillance

This paper develops a method to label alpha synuclein fibrils with fluorophores for tracking their structure and function in cells.

Preservation of dopamine neurotransmission during nigrostriatal neuron loss in rat Parkinson model: evidence for increased dopamine signaling in substantia nigra

The paper investigates compensatory mechanisms in dopamine signaling during nigrostriatal neuron loss in a rat Parkinson model, finding that dopamine levels are preserved in the substantia nigra despite significant TH loss.

Redefining Parkinson's Disease by Dysregulated Genetic Networks in Distinct Cell Types

This paper identifies six PD subgroups based on cell-type-specific genetic networks and links NRG6 to reduced myelin integrity in oligodendrocytes.

A molecular atlas of cell-type specific signatures in the parkinsonian striatum.

This study maps cell-type specific transcriptional changes in the parkinsonian striatum across species, identifying vulnerable and resilient cell types.

Prokineticin-2 Upregulates GDNF in Astrocytes and Pharmacological Modulation of PK2 Receptors offers Neuroprotection in Experimental Models of Parkinson's Disease

This study shows that PK2 signaling increases GDNF in astrocytes and that modulating PK2 receptors protects neurons in Parkinson's disease models.