Single cell eQTL mapping reveals convergent glial–neuronal risk architecture in Parkinson’s disease
By onPopulation-scale, disease-context aware meta single-nucleus eQTLs mapping (N 1,197) in nine cell types from cortex and substantia nigra identifies 125 risk genes and cell types for PD GWAS signals.
CREsted: modeling genomic and synthetic cell-type-specific enhancers across tissues and species
By onCREsted, a sequence-based deep learning model, analyzes genomic regulatory code, decodes enhancer grammar, and designs synthetic enhancers. It preprocesses single-cell data, models chromatin accessibility, and compares cell states across tissues.
A druggable ATP13A3–antizyme switch controls adaptive polyamine uptake in cancer
By onCellular polyamine depletion for cancer treatment is hindered by compensatory uptake. ATP13A3, not ATP13A2, is the key polyamine importer affected by DFMO. Antizyme inhibits uptake by ATP13A3, suggesting a targetable strategy for cancer therapy.
A single Citrobacter rodentium infection in Pink1 knockout and wild type mice leads to regional blood-brain-barrier perturbation and limited microglial activation without dopamine neuron axon terminal loss
By onResearch suggests immune system activation may contribute to Parkinson’s disease development. Mild infections can increase BBB permeability, triggering brain inflammation in genetically susceptible individuals, potentially leading to PD pathology.
STING dampens the unfolded protein response to enable the presentation of self antigens on MHC-I during inflammation
By onSTING pathway regulates antigen presentation through the UPR, impacting immune response in PD and autoimmune diseases. Targeting STING and UPR could be therapeutic.
An LRRK2 variant blocks NCOA4 trafficking upon iron overload, leading to ferroptotic death
By onWe examined the impact of mutant LRRK2-G2019S on iron homeostasis within a model macrophage cell line. Results revealed a dysregulation of iron-related proteins in steady state and a complete block in the degradation of the ferritinophagy NCOA4.
Thalamus orchestrates local acetylcholine-dependent dopamine release in the learning striatum
By onThalamic input can trigger dopamine release in the striatum during motor learning, likely reflecting action vigor rather than motor error. Changes in this mode of dopamine release may contribute to motor and non-motor symptoms of PD.
Cryo-EM structure of soluble VPS13C suggests its regulation by a conformational switch and by calmodulin
By onStructural studies of the Parkinson's protein VPS13C provide a molecular basis for understanding its function and regulation.
Q-DOAS: A Proximity Quenching Assay for Real-Time Detection of Early Protein Aggregation Events
By onWe describe Q-DOAS, a plate-reader assay that quantifies protein self-assembly in real time via proximity-quenching of a single, site-specifically conjugated dye (BODIPY-TMR), and which allows quantification of pre-amyloid oligomers.
Spermidine suppresses glial inflammation and parkinsonian abnormalities in ATP13A2 deficiency
By onPathogenic variants in ATP13A2 cause Kufor-Rakeb syndrome & early-onset parkinsonism. Spermidine supplementation rescues symptoms by counteracting microglia dysfunction & improving neuronal integrity.
NERINE reveals rare variant associations in gene networks across phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson’s disease
By onNERINE is a rare variant association test that links rare genetic variation with gene network topology to improve discovery power in complex diseases. NERINE implicates an α-synuclein/prolactin stress-response in Parkinson’s disease.
Regulation of the proteasome 20S core particle by the Parkinsonism-associated Proteins FBXO7 and PI31
By onGenetic forms of PD are associated with variants in FBXO7 and PI31. Combining biochemical and structural approaches, we describe the proteasome interaction of these proteins and map disease variants to disruption of proteasome interaction.
Cell-autonomous and non-cell-autonomous drivers of dopamine neuron vulnerability in Parkinson’s disease
By onThis review examines evidence for cell-autonomous mechanisms and non-cell-autonomous processes arising from glial and peripheral immune cells and how these pathways can converge to create chronic cellular stress and trigger cell death mechanisms.
Fluorescence-Gated Flow Cytometry Approach for Measuring Lipid Flippase Activity in Mammalian Cells
By onP4-ATPase lipid flippases create lipid asymmetry in cells. A new strategy using NBD-lipid uptake assays improves sensitivity and analysis of ATP11C function. This method enhances studying regulatory interactions in mammalian cells.
Para-subthalamic nucleus adjoins subthalamic nucleus and medial forebrain bundle, major DBS-targets in Parkinsons disease, OCD, and depression
By onThe para-STN is a poorly-defined region near critical DBS targets for PD. Here, we construct anatomical maps of para-STN and STN in multiple species using novel molecular markers in conjunction with FISH and light-sheet microscopy.
Structural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress
By onCryo-ET showed protein aggregates, altered cristae, and reduced ribosome complexes in stressed mitochondria. Mitochondrial Hsp60 undergoes conformational changes to aid in protein folding, shedding light on mitochondrial proteostasis mechanisms.
Excitatory synaptic structural abnormalities produced by templated aggregation of α-syn in the basolateral amygdala
By onPD and DLB involve α-syn inclusions in the amygdala affecting cognition and emotions. Cortico-amygdala synapses with α-syn aggregates show increased volume of synapses, potentially contributing to behavioral impairments.
Protocol for efficient CRISPRi-mediated silencing of retrotransposons in human pluripotent stem cells
By onThis methods paper outlines silencing transposable elements in hiPSCs using CRISPRi. Describes gRNA design, validation via multiome approach. Enables functional studies on TE transcription in hiPSC models.
Behavioral screening defines the molecular Parkinsonism-related subgroups in Drosophila
By onWe created a new collection of 24 genetically well-controlled Drosophila models of familial forms of parkinsonism. Using unbiased behavioral screening and machine learning we identified three clusters of mutants that converge.
Integrating Long-Read Structural Variant Analysis with single-nucleus RNA-seq to Elucidate Gene Expression Effects in Disease
By onLong-read sequencing in PD brain samples identified 74,552 structural variants. Integrating RNA sequencing data revealed SVs near PD-related genes impacting cell type-specific expression, highlighting the importance of SVs in complex diseases.
