Defect in hematopoiesis and embryonic lethality at midgestation of Vps13a/Vps13c double knockout mice
By onVPS13 proteins facilitate lipid transfer at membrane contact sites. VPS13A and VPS13C double knockout causes embryonic death due to impaired erythropoiesis and innate immunity activation.
Characterizing Parkinson’s Disease Clinical and Biomarker Interactions in REM Sleep Behavior Disorder
By ona-syn SAA positivity, DaT positivity, and hyposmia are highly associated with each other. MDS Prodromal PD Probability scores may be useful predictors of near-term progression, and thus as a stratification factor in clinical research study design
Inflamed Microglia like Macrophages in the Central Nervous System of Prodromal Parkinson′s Disease
By onWe investigated the role of inflammation in the pathogenesis of prodromal PD performing single-cell RNAseq analysis of CSF and blood from 111 individuals.
Generation of knock-in Cre and FlpO mouse lines for precise targeting of striatal projection neurons and dopaminergic neurons
By onTo enable precise genetic targeting of key neuronal populations in the basal ganglia, we generated and characterized five knock-in mouse lines: Drd1-Cre, Adora2a-Cre, Drd1-FlpO, Adora2a-FlpO, and DAT-FlpO.
EVscope: A Comprehensive Bioinformatics Pipeline for Accurate and Robust Analysis of 1 Total RNA Sequencing from Extracellular Vesicles
By onEVscope is a bioinformatics pipeline for processing EV RNA-seq datasets, improving read assignment with an EM algorithm. It generates BigWig files, corrects gDNA contamination, and infers RNA origins. The pipeline includes 19 RNA biotypes.
Striatal lateral inhibition regulates action selection in a mouse model of levodopa-induced dyskinesia
By onLateral inhibition in the striatum may help select actions and suppress alternatives. We identify chronic changes in the strength of striatal lateral inhibitory synapses in a mouse model of Parkinson's disease with levodopa-induced dyskinesia.
Repetitive Levodopa Treatment Drives Cell Type-Specific Striatal Adaptations Associated With Progressive Dyskinesia in Parkinsonian Mice
By onLevodopa treatment for Parkinson's leads to levodopa-induced dyskinesia (LID). Research shows LID worsening is linked to potentiation of responses in D1-/D2-MSNs, driven by strengthened glutamatergic synapses on D1-MSNs and reduced D2R sensitivity.
Corticonigral projections recruit substantia nigra pars lateralis dopaminergic neurons for auditory threat memories
By onAuditory and temporal cortexes send strong excitatory signals to substantia nigra pars lateralis dopamine neurons, impacting threat conditioning. Inhibiting this pathway impairs memory retrieval, revealing its role in threatening behaviors.
Presynaptic GABAA receptors control integration of nicotinic input onto dopaminergic axons in the striatum
By onDopaminergic neuron axons have GABAARs and nAChRs that influence DA release. GABAAR antagonism enhances nAChR activity, while picrotoxin inhibits nAChRs, revealing GABAARs' role in regulating nicotinic input onto DA axons.
Bidirectional regulation of glycoprotein nonmetastatic melanoma protein B by β-glucocerebrosidase deficiency in GBA1 isogenic dopaminergic neurons from a patient with Gaucher disease and parkinsonism
By onGBA1 variants increase risk for synucleinopathies due to misfolded GCase and lipid accumulation from reduced enzyme activity. Our Study using iPSCs links lipid levels to PD risk marker GPNMB, refining GBA1 pathogenicity.
A lipid transfer-dependent feedback loop activates ATG9A compartments in autophagy initiation
By onPhagophore formation requires ATG9, ATG2 and PI3KC3-C1. Authors show that ATG2 is crucial for PI3P appearance on ATG9A compartments with little PI, suggesting a lipid transfer-driven feedback loop supporting lipid transfer and ATG8 lipidation.
Structural basis for binding of RILPL1 to TMEM55B reveals a lysosomal platform for adaptor assembly through a conserved TBM motif
By onInherited mutations in VPS35 and LRRK2 cause Rab GTPase hyperphosphorylation. TMEM55B on lysosomes interacts with RILPL1 through a specific motif, forming complexes with various proteins, revealing new insights into lysosomal function.
Neuromodulator control of energy reserves in dopaminergic neurons
By onNeurons, are vulnerable to metabolic changes. Dopamine helps regulate glycogen storage providing resilience to stress. Loss of this regulation can make dopamine neurons hypersensitive to fuel deprivation, potentially leading to neurodegeneration.
Integrated Representations of Threat and Controllability in the Lateral Frontal Pole
By onEmotions can strongly influence behavior, as seen in PD paradoxical kinesia. Here, we demonstrate that anticipating threats enhances motor accuracy through interactions between the amygdala and the anterior pole of the lateral prefrontal cortex.
A single Citrobacter rodentium infection in Pink1 knockout and wild type mice leads to regional blood-brain-barrier perturbation and glial activation without dopamine neuron axon terminal loss
By onWe tested whether a gut infection causes blood-brain barrier permeability and brain inflammation. Results showed increased BBB permeability in specific brain regions at 26 days while tight-junction and dopamine related proteins remained unchanged
LRRK2G2019S acts as a dominant interfering mutant in the context of iron overload
By onUsing a model macrophage cell line we showed that LRRK2-G2019S mutation affects iron homeostasis by dysregulating iron-related proteins and blocking ferritinophagy in iron overload conditions, suggesting a role in iron dysregulation in PD.
Robust analytical methods for bis(monoacylglycero)phosphate profiling in health and disease
By onBMP is a crucial phospholipid in lysosomes, impacting metabolic balance and linked to neurodegenerative diseases. LC-MS methods are detailed for accurate BMP analysis, utilizing structural differences and a new CLN5 function for profiling.
AutoMorphoTrack: An Automated Python Package for Organelle Morphology, Motility, and Colocalization Analysis in Live-Cell Imaging
By onAutoMorphoTrack is a Python package for analyzing organelle dynamics in live-cell imaging data. It automates detection, classification, tracking, and colocalization of mitochondria and lysosomes, enabling reproducible and quantitative analysis.
