Parkinson's Disease Mechanisms and Treatments

Alpha-synuclein fibrils induce budding of mitochondrial-derived vesicles

This study shows that alpha-synuclein fibrils cause mitochondrial-derived vesicle budding and structural changes in mitochondria, linking alpha-synuclein aggregation to mitochondrial toxicity.

α-Synuclein and γ-Tubulin Cooperatively Regulate Activity-Evoked Presynaptic Microtubule Nucleation to Gate Dopamine Release

This study identifies a mechanism by which α-synuclein and γ-tubulin cooperatively regulate activity-evoked presynaptic microtubule nucleation to control dopamine release.

Emergence of Task-Related Motor Cortical Dysfunction in Mice with Progressive Parkinsonism

This study examines M1 circuit dysfunction in MitoPark mice during progressive Parkinsonism, finding reduced cellular activity and impaired neuronal coactivation linked to motor deficits.

An N-acylphosphatidylethanolamine-LRRK2 axis controls lysosomal homeostasis in Parkinson s disease

This study identifies NAPEs as regulators of LRRK2 and lysosomal function in Parkinson's disease, showing that boosting NAPEs reduces LRRK2 activity and clears alpha-synuclein aggregates.

Distinct and Combined Interferon-α/β-receptor-1 Loss in Neurons and Astrocytes Disrupt Brain Energy Metabolism and Drive Parkinsonian Dementia

This paper shows that loss of IFNAR1 in neurons and astrocytes disrupts brain energy metabolism and leads to Parkinsonian dementia-like features in mice.

Levodopa increases substantia nigra iron: implications for Parkinson's disease

This study shows levodopa increases iron in the substantia nigra of rats, independent of dopamine neurons, suggesting treatment-related iron accumulation in Parkinson's disease.

Therapeutic Peptide SS-31 Modulates Membrane Binding and Aggregation of Alpha-Synuclein and Restores Impaired Mitochondrial Function

This study shows SS-31 reduces alpha-synuclein membrane binding, aggregation, and mitochondrial dysfunction in neuroblastoma cells.

In-cell cryo-electron tomography reveals differential effects of type I and type II kinase inhibitors on LRRK2 filament formation and microtubule association

This study uses in-cell cryo-electron tomography to compare how type I and type II kinase inhibitors affect LRRK2-I2020T filament formation and microtubule association in cells.

Blm10/PA200-activated 20S proteasomes promote α-synuclein degradation and bypass proteasome inhibition in Parkinson disease models

This study shows that Blm10/PA200 activates 20S proteasomes to degrade α-synuclein and resist inhibition, improving proteostasis in Parkinson's disease models.

LRRK2 mutations block NCOA4 trafficking upon iron overload leading to ferroptotic death

The paper shows LRRK2 mutations impair NCOA4 trafficking during iron overload, causing ferroptotic cell death in macrophages.

Curli Carrier Burden: a quantitative trait-level microbiome index for amyloidogenic bacterial signals in Parkinsons disease gut metagenomes

The paper introduces Curli Carrier Burden (CCB), a microbiome index quantifying amyloidogenic bacterial signals in Parkinson's disease gut metagenomes, and validates its utility across multiple cohorts.

The phosphorylation status of LRRK2 at the S910/S935 cluster determines its sensitivity to activation by RAB29

This study shows that dephosphorylation of LRRK2 at the S910/S935 cluster increases its sensitivity to activation by RAB29, leading to hyperactivation and centrosome cohesion deficits.

Antibody treatment targeting nitrated alpha-synuclein counteracts protein spreading pathology

This study shows that targeting nitrated alpha-synuclein with an antibody reduces pathology in Parkinson's disease models and correlates with increased levels in Parkinson's patients.

Alternative Import-Channels And Destinations Of Mitochondrial PINK1 Controlled By Trans-Membrane-Domain Structural Plasticity

The paper investigates alternative import pathways and destinations of PINK1 in mitochondria, revealing structural plasticity of its trans-membrane domain that influences its fate.

iPSC-derived extracellular vesicles rescue deficits in human and mouse models of Parkinsons disease

The paper shows that extracellular vesicles from healthy iPSCs can reverse Parkinson's disease-related deficits in human and mouse models.

Multiparametric MRI and imaging transcriptomics reveal molecular and cellular correlates of neurodegeneration in experimental multiple system atrophy

The paper uses imaging transcriptomics in a mouse model of MSA to link MRI patterns with gene expression, identifying molecular correlates of neurodegeneration.

Deconvolving the structural heterogeneity of alpha-Synuclein in vitro and in situ

This paper develops a method to quantitatively analyze the structural states of alpha-synuclein in vitro and in situ, revealing conformational changes in yeast and human neurons.

Microglial Foxo3 shapes dopaminergic vulnerability in Parkinson disease

This study identifies Foxo3 as a key regulator of dopaminergic vulnerability through microglial mechanisms, showing that baseline microglial state, rather than acute transcriptional responses, determines neurodegeneration in Parkinson's disease.

Proximity proteomics reveals a co-evolved LRRK2-regulatory network linked to centrosomes

This study identifies a LRRK2-regulatory network through proximity proteomics and structural analysis, showing its link to centrosomes and how its conformation and activity state influence interactions.

Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation

This study shows that PPM1H knockout disrupts axonal autophagy and increases alpha-synuclein aggregation in neurons, linking LRRK2 hyperactivity to Parkinson disease pathology.

Directional Gene-Level Concordance and Methodological Constraints in Blood Transcriptomic and DNA Methylation Studies of Parkinson's Disease

This study evaluates reproducibility of transcriptomic and DNA methylation findings in Parkinson's disease across multiple cohorts and analytical pipelines, finding directional consistency is more reliable than gene-identity overlap.

GLP-1 analogs restore inflammatory, mitochondrial and intercellular signaling networks in the SncaG51D/G51D knock-in mouse model of Parkinson's disease

GLP-1 analogs improve motor and non-motor deficits and reduce gliosis and insoluble α-synuclein in a Parkinson's disease mouse model.

Reduced cortical VPS26B levels are associated with altered glutamate receptor expression and synaptic protein loss in the primary motor cortex of a Parkinsonian mouse model

This study shows reduced VPS26B in the primary motor cortex of a Parkinsonian mouse model correlates with decreased glutamate receptor and synaptic protein levels, and impaired motor performance.

GPNMB and glycosphingolipid measurements in cerebrospinal fluid and plasma from Parkinson's disease patients

The paper measures GPNMB and glycosphingolipid levels in CSF and plasma from PD patients and controls, finding sex-based differences and associations with PD biomarkers.

Oligodendrocyte subtype diversity underlines clinical progression in Parkinsons disease

The paper identifies oligodendrocyte subtype changes in Parkinson's disease across species, linking them to disease progression and clinical outcomes.

Protocol for using an ELISA to detect total α-synuclein levels in Drosophila melanogaster lines expressing human α-synuclein point mutations

The paper develops an ELISA to measure total α-synuclein levels in Drosophila expressing human α-synuclein mutations and identifies mutation-dependent differences and potential therapeutic modulators.

α-Synuclein aggregates induce mitochondrial damage and trigger innate immunity to drive neuron-microglia communication

This study shows that α-synuclein aggregates cause mitochondrial damage and activate innate immunity, leading to neuron-microglia communication via TNTs and promoting disease progression in Synucleinopathies.

Regulation between LRRK2 and PP2A signaling in cellular models of Parkinsons disease

This study identifies a regulatory feedback loop between LRRK2 and PP2A phosphatases in Parkinson's disease, showing that LRRK2 phosphorylates PP2A to disrupt its function and contribute to neuronal death.

PINK1/Parkin-dependent mitophagy mediates astrocytic inflammatory responses to mitochondrial damage

This study shows that mitochondrial damage in astrocytes triggers inflammatory responses via PINK1/Parkin-dependent mitophagy, leading to cytokine release and neuroinflammation in Parkinson's disease.

Single-cell quantification of the iron-neuromelanin balance in dopaminergic neurons across the lifespan

The paper quantifies iron and neuromelanin in dopaminergic neurons across chimpanzee lifespan, finding stable iron-to-neuromelanin ratios and no evidence of saturation or increased toxicity with age.