Parkinson's Disease Mechanisms and Treatments

DJ-1 deficiency in SH-SY5Y cells reveals dysregulated networks of genes and pathways involved in neuronal function and disease

This study investigates the effects of DJ-1 deficiency in SH-SY5Y cells, identifying dysregulated genes and pathways linked to neuronal function and neurodegenerative diseases.

Sex-Stratified Multi-Omics Identifies Sexually Dimorphic Molecular Targets in Parkinsons Disease

This study identifies sex-specific molecular targets in Parkinson's disease through multi-omic integration, revealing sexually dimorphic pathways and gene associations.

Rare variants alter mitochondrial lipid homeostasis and neuronal excitability in PD patient-derived dopaminergic neurons

This study investigates how rare genetic variants in PD patients affect mitochondrial lipid homeostasis and neuronal excitability using patient-derived dopaminergic neurons.

Ferroptosis links α-synuclein pathology across brain and skeletal muscle in Parkinsons disease

This study identifies ferroptosis as a shared mechanism linking brain and skeletal muscle pathology in Parkinson's disease through α-synuclein-TFRC interactions.

Coordination of Anle138b to Silver Results in Selective Reduction of a C-terminal truncated Alpha-synuclein Protein and Increased Aggregate Size

The paper investigates how Anle138b coordination with silver affects alpha-synuclein aggregation, showing reduced C-terminal truncation and increased aggregate size.

Dimerisation and twist reversal of the Lewy fold in α-synuclein mutants with Parkinson's disease and dementia

The paper reports the structures of α-synuclein filaments from individuals with Parkinson's disease and dementia, revealing differences in dimerisation and twist reversal between pathogenic and non-pathogenic variants.

Determination of α-Synuclein Protein Interactions by μMap Photo-proximity Labeling

This study uses μMap photo-proximity labeling to compare the interactomes of α-synuclein monomers and fibrils in mouse brain lysate to investigate synucleinopathy mechanisms.

WDR44 drives de novo α-synuclein aggregation at the lysosomal membrane and promotes neuronal dysfunction in Parkinson's Disease

This study identifies WDR44 as a driver of de novo α-synuclein aggregation at the lysosomal membrane, linking early aggregation events to neuronal dysfunction in Parkinson's Disease.

ATP13A2 Loss of Function-Driven Polyamine Dysregulation Induces SAM Depletion and Epigenetic Astrocyte Toxicity

The paper shows ATP13A2 loss of function disrupts polyamine metabolism, leading to SAM depletion and epigenetic astrocyte toxicity, which contributes to Parkinson's disease.

Neural cell state modulation by PARK2 and dopaminergic neuroprotection by small molecule Parkin agonism

This study shows that Parkin is essential for neuronal differentiation and survival, and small molecule Parkin agonists like FB231 protect dopaminergic neurons in Parkinson's disease models.

Astrocytic FABP5 drives non-cell-autonomous oligodendrocyte injury in multiple system atrophy by promoting TNF signaling and ferroptotic stress

This study identifies FABP5 as a key driver of astrocyte-mediated oligodendrocyte injury in MSA by promoting TNF signaling and ferroptotic stress.

Aberrant FICD-mediated AMPylation drives α-Synuclein pathology and overall protein dyshomeostasis in dopaminergic neurons in Parkinson's disease

This study shows that FICD-mediated AMPylation contributes to Parkinson's disease by promoting α-synuclein aggregation and protein dyshomeostasis in dopaminergic neurons.

TNF-α disrupts the malate-aspartate shuttle, driving metabolic rewiring in iPSC-derived enteric neural lineages from Parkinson's Disease patients

This study shows TNF-α disrupts the malate-aspartate shuttle in iPSC-derived enteric neural cells from PD patients, causing metabolic shifts and mitochondrial dysfunction, which can be reversed by targeting glutamate metabolism.

Single-cell RNA sequencing of peripheral blood cells identifies transcriptomic signatures in Parkinson's disease

This study uses single-cell RNA sequencing to identify immune cell-specific gene expression signatures and sex differences in Parkinson's disease patients compared to healthy controls.

DAPK1-mediated parkin inactivation enhances neurotoxicity via MITOL-dependent degradation

This study shows DAPK1 phosphorylates parkin, promoting its degradation via MITOL and enhancing neurotoxicity in Parkinson's disease.

Autophagy Dysfunction in iPSCs-Derived Neurons and Midbrain Organoids Carrying a SNCA Triplication

This study uses iPSC-derived neurons and midbrain organoids with SNCA triplication to show autophagy defects correlate with -Synuclein pathology and neuronal loss in Parkinson's disease.

A new therapeutic approach for Parkinson's disease: dual targeting of alpha-Synuclein aggregation and microglial function by the novel immunomodulator 3-Monothiopomalidomide

This paper evaluates 3MP, a novel immunomodulator, showing it reduces alpha-Synuclein aggregation and microglial inflammation in vitro and in vivo, offering a dual-target therapeutic approach for Parkinson's disease.

Transposable elements as new players to decipher sex differences in Parkinson Disease

The paper analyzes transposable elements in Parkinson Disease datasets to build a cell-type specific atlas and explore their role in sex differences.

Identification of Parkinson's disease-associated regulatory variants in human dopaminergic neurons reveals modulators of SCARB2 and BAG3 expression

The paper identifies Parkinson's disease-associated regulatory variants in human dopaminergic neurons and shows they modulate SCARB2 and BAG3 expression.

Single-cell resolution uncovers cell type-specific dysregulation in Parkin-deficient neuron-microglia co-cultures

The paper uses single-nucleus RNA sequencing to identify cell type-specific dysregulation in Parkin-deficient neuron-microglia co-cultures, revealing distinct pathway disturbances in dopaminergic neurons and microglia.

Blunted response of caudal locus coeruleus to arousing stimuli in Parkinson's Disease

This study shows that Parkinson's Disease causes reduced structural and functional activity in the caudal locus coeruleus, linked to non-motor symptoms.

Mitochondrial DNA damage in substantia nigra parscompacta astrocytes exacerbates dopaminergic neuron lossin a 6-hydroxydopamine mouse model of parkinsonism

This study shows that mitochondrial DNA damage in SNc astrocytes worsens dopaminergic neuron loss in a Parkinson's disease mouse model.

Membrane Interfacial Potential Governs Surface Condensation and Fibrillation of α-Synuclein in Neurons

This study shows that lipid membrane interfaces drive α-synuclein condensation and fibrillation at low concentrations, revealing a mechanism for its propagation in neurodegeneration.

Inflammatory signaling differentially changes chromatin accessibility and gene expression of the PD- associated kinase LRRK2 between human and mice

The paper shows that inflammatory signaling affects LRRK2 regulation differently in human and mouse models, highlighting species-specific regulatory mechanisms.

Combination of alpha-synuclein aggregation inhibitor anle138b and ER stress inhibitor AMG PERK 44 increases neuroprotection in Parkinson's disease organoid model

The paper shows that combining anle138b and AMG44 enhances neuroprotection in a Parkinson's disease organoid model by reducing alpha-synuclein aggregation and ER stress.

Neuronal overexpression of mouse potassium channel subunit Kcnn1 in A53T α-synuclein mice more than doubles median survival time, associated with suppression of phospho-S129 α-synuclein formation

This study shows that overexpressing Kcnn1 in A53T α-synuclein mice significantly increases survival and reduces phospho-S129 α-synuclein accumulation.

Calcium modulates intramolecular long-range contacts to form a polymorphic α-synuclein A53T fibril

This study investigates how calcium ions affect the structure and aggregation of the A53T mutant of α-synuclein, revealing structural changes in fibril formation.

Stools and stool-derived extracellular vesicles from patients with Parkinson`s disease show alpha-4 synuclein seeding activity

This study shows that stool-derived extracellular vesicles from Parkinson's disease patients have alpha-synuclein seeding activity detectable by seed amplification assay, with improved sensitivity after pre-incubation with recombinant monomeric alpha-synuclein.

Zhi-Shi-Huang-Wu slows Parkinson's disease progression in transgenic C. elegans models

The paper evaluates the neuroprotective effects of a traditional Chinese medicine formula, Zhi-Shi-Huang-Wu, in Parkinson's disease models using transgenic C. elegans.

The alpha-Synuclein Proteostasis Network and its Translational Applications in Parkinson's disease

The paper maps the alpha-synuclein proteostasis network in Parkinson's disease, defines a proteostasis activity score, and applies it to drug repurposing and target identification.