Parkinson's Disease Mechanisms and Treatments

Peripheral inflammation mediates midbrain Lrrk2 kinase activity via Rab32 expression

This study identifies Rab32 as a mediator linking peripheral inflammation to Lrrk2 kinase activity in microglia, with Tfe3 regulating Rab32 expression and Lrrk2 activation.

Post-traumatic stress disorder and REM-sleep behavior disorder: exploring genetic associations and causal links

The paper investigates genetic and causal links between post-traumatic stress disorder and rapid-eye-movement sleep behavior disorder using polygenic risk scores, genetic correlation, and Mendelian randomization analyses.

TDP-43 loss of function drives aberrant splicing in Parkinson's disease

The paper identifies splicing dysregulation in Parkinson's disease linked to TDP-43 loss of function and shows its association with genetic mutations and cellular models.

Inhibition of Indirect Pathway Activity Causes Abnormal Decision-Making In a Mouse Model of Impulse Control Disorder in Parkinson's Disease

This study develops a mouse model of Parkinson's disease with impulse control disorder and shows that inhibiting indirect pathway neurons exacerbates abnormal decision-making.

Alpha-Synuclein aggregates inhibit ESCRT-III through sequestration and collateral degradation

This study shows that alpha-synuclein fibrils sequester and degrade ESCRT-III proteins, leading to endolysosomal damage and increased alpha-synuclein aggregation.

The Morphology of α-Synuclein Fibrils Changes during Formation, Storage, and upon Exposure to Ligands

This study investigates how α-synuclein fibril morphology changes during formation, storage, and exposure to ligands, showing continuous structural evolution and ligand-induced morphological shifts.

LRRK2 G2019S mutation incites increased cell-intrinsic neutrophil effector functions and intestinal inflammation in a model of infectious colitis

This study shows that the LRRK2 G2019S mutation enhances neutrophil effector functions and drives intestinal inflammation in a mouse model of infectious colitis.

The LRRK2 p.A419V variant associates with risk of Parkinson disease in the East Asian population and an evaluation on age of onset

The paper identifies the LRRK2 p.A419V variant as a significant risk factor for Parkinson's disease in East Asian populations and explores its association with age of onset.

Molecular aging is the main driver of Parkinson's Disease

This study shows that aging processes drive Parkinson's Disease in a mouse model, independent of alpha-synuclein oligomers, by targeting CDC42 activity.

PINK1 regulates cholesterol homeostasis via SCAP phosphorylation in human dopaminergic neurons

This study shows that PINK1 regulates cholesterol homeostasis in human dopaminergic neurons by phosphorylating SCAP, and restoring cholesterol levels rescues defects in neurotransmitter uptake.

Microglial activation and alpha-synuclein oligomers drive the early inflammatory phase of Parkinson's disease

The paper identifies microglial activation and alpha-synuclein oligomers as drivers of early neuroinflammation in Parkinson's disease using transcriptomic and aggregate profiling in early-stage brain samples.

Novel in situ seeding immunodetection assay uncovers neuronal-driven alpha-synuclein seeding in Parkinson's disease

The paper introduces an in situ seeding immunodetection assay to visualize alpha-synuclein and tau seeding activities with high spatial resolution in intact tissues, revealing neuron-driven alpha-synuclein seeding in Parkinson's disease before clinical symptoms.

Contrasting patterns of interleukin signalling in LRRK2 and idiopathic Parkinson's

The paper compares inflammatory markers in sporadic and LRRK2-associated Parkinson's using transcriptomics and proteomics to identify molecular differences and a protein cluster linked to tau pathology.

Region-specific variations in the cerebrovasculature underlie disease progression in Parkinson's disease

This study identifies region-specific vascular changes in Parkinson's disease brains, showing reduced aquaporin-4 and increased string vessels correlate with disease duration.

A brain-shuttled antibody targeting alpha synuclein aggregates for the treatment of synucleinopathies

This paper presents preclinical data on a bispecific antibody, SAR446159, designed to target alpha-synuclein aggregates and cross the blood-brain barrier for treating synucleinopathies.

Suppression and modulation mechanism underlying the flavonoid-induced inhibition of fibrillation of α-synuclein

This study investigates how Cyanidin inhibits α-synuclein fibrillation by modulating nucleation and promoting the formation of less-hydrophobic, SDS-resistant oligomers.

M5 positive allosteric modulation alleviates parkinsonian motor deficits

This study investigates the potential of M5 positive allosteric modulators to alleviate parkinsonian motor deficits without causing dyskinesia or impairing L-DOPA efficacy.

The Quest for a Universal Parkinson's Transcriptomics Signature is Derailed by Inherent Variability between Patients

This study evaluates the reproducibility and clinical utility of blood mRNA-based gene signatures for Parkinson's disease classification, finding modest performance due to inter-individual variability.

α-Synuclein driven cell susceptibility in Parkinson's disease

The paper maps α-synuclein oligomers in Parkinson's disease brain tissue to identify aggregation-susceptible cells and proposes a population-level model for early pathology.

Parkinson's disease and multiple system atrophy are gateways to RFC1-related disorders

The paper screens patients with parkinsonism for RFC1 gene expansions and finds that Parkinson's disease and multiple system atrophy can be gateways to RFC1-related disorders.

From berries to brain: Assessing the impact of (poly)phenols in the MPTP mouse model of Parkinson's disease

This study shows that a polyphenol-enriched berry diet reduces motor deficits, protects dopaminergic neurons, and decreases inflammation in MPTP-intoxicated mice.

Multivalent interaction induces phase separation and formation of more toxic aggregates of α-syn in a yeast model of Parkinsons disease

This study investigates how multivalent interactions affect α-synuclein phase separation and toxicity in a yeast model of Parkinson's disease, identifying two distinct aggregation pathways with different fibril characteristics and toxicities.

Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype

The paper investigates synaptic changes and brain connectivity in a PD-like mouse model with depressive symptoms, finding early synaptic markers linked to -synuclein pathology.

LRRK2-mutant microglia and neuromelanin synergize to drive dopaminergic neurodegeneration in an iPSC-based Parkinson's disease model

LRRK2 G2019S iPSC-derived microglia exposed to neuromelanin, but not α-synuclein fibrils, reduce healthy dopaminergic neuron numbers in co-culture; ivermectin prevents this, and post-mortem midbrain supports it.

Glutamatergic synaptic resilience to overexpressed human alpha-synuclein

This study overexpresses human alpha-synuclein in rodent glutamatergic neurons and finds no significant impairment in synaptic function.

Reduction of a-synuclein aggregates by PIKfyve inhibition via TFEB-mediated lysosomal biogenesis in a Parkinson disease model

This study shows that PIKfyve inhibition reduces alpha-synuclein aggregates in a Parkinson's disease model by enhancing lysosomal biogenesis through TFEB activation.

Morphological profiling reveals neuroprotection via mitochondrial uncoupling in human dopaminergic neurons

The paper identifies compounds that restore morphology in Parkinson's disease neurons by targeting mitochondrial uncoupling.

Spreading alpha-Synuclein Oligomers Trigger Astrocyte Changes and Astrocyte-Glutamatergic Neuron system dysfunction in an Age-related Manner

The paper investigates how alpha-synuclein oligomers spread in a mouse model of Parkinson's disease, identifying age-related astrocyte changes and dysfunction in the astrocyte-glutamatergic neuron system.

Regulation of polyamine interconversion enzymes affects α-Synuclein levels and toxicity in a Drosophila model of Parkinsons disease

This study shows that manipulating polyamine interconversion enzymes in a Drosophila Parkinson's model affects alpha-synuclein levels and toxicity, suggesting a potential therapeutic target.

LRRK2 Kinase Activity Regulates Parkinson's Disease-Relevant Lipids at the Lysosome

This study shows that LRRK2 kinase activity affects BMP and GSL levels in lysosomes, linking lysosomal dysfunction to Parkinson's disease through changes in GCase activity and BMP accumulation.