End-product inhibition of the LRRK2-counteracting PPM1H phosphatase
By onPPM1H phosphatase reverses Rab GTPase phosphorylation by LRRK2 in Parkinson's disease. PPM1H binds Rab8A and Rab10 at an allosteric site, inhibiting phosphatase activity. Targeting this site may offer a therapeutic strategy.
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.
Dynamic basal ganglia output signals license and suppress forelimb movements
By onBasal ganglia is fundamental to motor control and dysfunction is linked to motor deficits. Our results demonstrate the existence and function of highly specific and temporally precise movement representations in basal ganglia output circuitry.
CREsted: modeling genomic and synthetic cell type-specific enhancers across tissues and species
By onDeep learning models decode genomic regulatory codes well, especially enhancers. CREsted enables end-to-end enhancer modeling, design, and analysis, proving effective across datasets and species through comprehensive training and evaluation.
HyDrop v2: Scalable atlas construction for training sequence-to-function models
By onSingle-cell chromatin accessibility data helps train deep learning models to decode enhancer logic. HyDrop v2 improves data generation across species, organs, and diseases, delivering results comparable to commercial platforms like 10x Genomics.
AI-directed voxel extraction and volume EM identify intrusions as sites of mitochondrial contact
By onThe AI-directed Voxel Extraction (AIVE) segmentation strategy combines AI predictions with image electron signals to confidently segment membrane boundaries. Authors identify a new category of Membrane contact Sites named Mitochondrial Intrusions.
Astrocytic polyamine transport by ATP13A4 tunes excitatory synaptic transmission
By onPolyamines are crucial for brain function. ATP13A4 is the main polyamine transporter in astrocytes, impacting astrocyte morphology, synapse formation, and neurodevelopment. Mutations in ATP13A4 are linked to neurodevelopmental disorders.
In situ cryo-ET visualization of mitochondrial depolarization and mitophagic engulfment
By onApplication of in situ cryo-electron tomography (cryo-ET) applied to visualize the consequences of mitochondrial depolarization at higher resolution.
PPM1M, a LRRK2-counteracting, phosphoRab12-preferring phosphatase with potential link to Parkinson’s disease
By onLRRK2 phosphorylates Rab GTPases linked to Parkinson's disease. PPM1M identified as a phosphatase reversing Rab phosphorylation, crucial in LRRK2 pathway. PPM1M mutation found in Parkinson's patients, suggesting a new therapeutic target.
EndoMAP.v1, a Structural Protein Complex Landscape of Human Endosomes
By onEarly endosomes regulate protein fate, sorting plasma membrane proteins for recycling or degradation. Cross-linking and computational analysis were used to create a human endosomal structural interactome, revealing potential regulatory mechanisms.
ATG2A engages Rab1a and ARFGAP1 positive membranes during autophagosome biogenesis
By onATG2A aids in autophagosome formation by localizing to extra-Golgi ARFGAP1 puncta with Rab1 during early stages. Rab1 is crucial for autophagy, and disruptions in autophagosome formation lead to accumulation of ARFGAP1 and Rab1a at ectopic sites.
Soluble Immune Factor Profiles in Blood and CSF Associated with LRRK2 Mutations and Parkinson’s Disease
By onThis preprint explores immune factors in Parkinson's disease linked to LRRK2 mutations. Serum showed elevated SDF-1 alpha and TNF-RII levels in LRRK2 carriers, while CSF had reduced immune markers. PD patients displayed reduced CSF inflammation.
Postsynaptic adaptations in direct pathway muscarinic M4-receptor signaling follow the temporal and regional pattern of dopaminergic degeneration
By onImbalances in dorsal striatum output in Parkinson's disease are driven by dopamine loss and disrupted acetylcholine signaling. These changes occur in response to dopamine loss, affecting M4 receptors in striatal neurons, crucial for PD progression.
Genetically encoded self-assembling synuclein for tunable Parkinsonian pathology in vitro and in vivo
By onThis paper describes the self-assembling synuclein (SAS) system, a genetically-encoded tool for inducing temporally-controllable, tunable PD pathology in a wide range of in vitro and in vitro models.
Network analysis of α-synuclein pathology progression reveals p21-activated kinases as regulators of vulnerability
By onMisfolded α-synuclein accumulation in PD leads to pathogenic processes. We mapped α-synuclein pathology in mice to identify vulnerable regions and potential therapeutic targets, highlighting group II PAK inhibitors as promising for treating PD.
Severe GBA1 variants drive the GBA-PD clinical phenotype: implications for counselling and clinical trials
By onVariants in the GBA1 gene are common genetic risk factors for Parkinson's disease. A study compared clinical phenotypes in GBA-PD and idiopathic PD patients, finding that only severe GBA-PD cases show a more severe clinical profile.
Exploring the relationship between GBA1 host genotype and gut microbiome in the GBA1L444P/WT mouse model: Implications for Parkinson disease pathogenesis
By onHeterozygous *GBA1* variants are common in Parkinson's disease. This study found no significant impact of the *GBA1* L444P variant on gut microbiome composition in mice, suggesting other factors may contribute to disease penetrance.
