Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration.
By onWe found that neddylation-inhibition triggers age-related features in PSC-derived neurons for modeling AD or PD. This strategy can induce late-onset phenotypes including degeneration when applied to DA neurons from PD- versus isogenic control PSCs.
Contextual AI models for single-cell protein biology
By onThis study describes PINNACLE a deep learning approach establish context dependent networks. PINNACLE is a key algorithm used in our ASAP project to provide cell type , age-or disease context to our experimental datasets.
Integrating population genetics, stem cell biology and cellular genomics to study complex human diseases
By onThis review describes current state-of-the art of pooled "village-style" hPSC-based assays. This is a major topic for disease modeling including PD and for linking disease with genetic and/or environmental risk and part of our experimental ASAP work.
SARS-CoV-2 infection causes dopaminergic neuron senescence.
By onThe ASAP-supported aspect of this study involves the DA neuron senescence work, and experiments using ASAP lines (isogenic a-SYN triplication) to assess interaction of genetic vulnerability with viral-induced senescence as PD penetrance factor.
PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection
By onUsing single-cell RNAseq in our PINK KO mouse model, we demonstrate that peripheral myeloid cells are the earliest highly dysregulated immune cell type followed by an aberrant T cell response shortly after infection.
The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications
By onThis article summarises the most up-to-date knowledge in pharmacomicrobiomics in PD, and discusses how the manipulation of gut microbiota represents a potential new therapeutic avenue for PD.
Cortico-basal ganglia plasticity in motor learning
By onThe cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is linked to movement. Here, the authors detail the cortico-basal ganglia plasticity in motor learning
Distinct spatially organized striatum-wide acetylcholine dynamics for the learning and extinction of Pavlovian associations
By onStriatal acetylcholine (ACh) signaling in mice shows opposing changes across different regions, with positive and negative prediction errors encoded in anterior dorsal striatum.
More of less: Novel multi-ome profiling of single human neurons
By onThis review describes a novel single-cell multi-omic method, simultaneously profiling transcriptome, DNA methylome, and chromatin accessibility, to shed light on human neurons.
Biochemical Fractionation of Human α-Synuclein in a Drosophila Model of Synucleinopathies
By onSynucleinopathies involve α-synuclein accumulation in Lewy Bodies. A-synuclein in Drosophila helps understand its effects. A method using detergents and sonication separates soluble/insoluble forms of human α-synuclein from fly brains aiding research
Neither alpha-synuclein fibril strain nor host murine genotype influences seeding efficacy
By onParkinson’s disease (PD) involves motor symptoms and αsyn aggregation. GBA1 mutations may worsen PD progression. Testing showed similar αsyn spread regardless of genotype or αsyn strain, with unique interactions found in GBA-PD brains.
Alpha-synuclein aggregates are phosphatase resistant
By onCIAP pretreatment has important implications for the mechanism of PSER129-accumulation in the synucleinopathy brain and provides a simple experimental method to differentiate endogenous from aggregated PSER129.
Pathogenic LRRK2 mutations cause loss of primary cilia and Neurturin in striatal Parvalbumin interneurons
By onLRRK2 mutations in Parkinson's disease inhibit primary cilium formation in specific brain cells, affecting movement control. Parvalbumin interneurons lose cilia, impacting response to signals and neuroprotection for dopamine neurons.
scNAT: a deep learning method for integrating paired single-cell RNA and T cell receptor sequencing profiles
By onThe authors developed scNAT, a deep learning method that integrates paired scRNA-seq and scTCR-seq data to represent data in a unified latent space for downstream analysis.
Gut instincts in neuroimmunity from the eighteenth to twenty-first centuries
By onIn this review, the authors revisit the history of gut-brain interactions in science and medicine, which dates back to at least the eighteenth century, and outline how concepts in this field have shifted and evolved across eras.
State-of-the-art review of the clinical research on menopause and hormone replacement therapy association with Parkinson’s disease: What meta-analysis studies cannot tell us
By onStudies have shown varying effects of menopause on Parkinson's disease in part due to differences in study design. This review provides an overview of the clinical literature thus far and provides considerations for future studies.
Nigrostriatal tau pathology in parkinsonism and Parkinson’s disease
By onStudy focuses on mild motor deficits not meeting Parkinson's criteria. Nigrostriatal system changes occur regardless of alpha-synuclein presence, hinting at tau-mediated dopaminergic neurodegeneration initiation. Tau pathology seen in affected groups
Distributed dopaminergic signaling in the basal ganglia and its relationship to motor disability in Parkinson’s disease
By onDegeneration of dopaminergic neurons in the brain causes PD motor symptoms. Recent research shows dopamine's role in basal ganglia regions beyond striatum impact movement control. Restoring dopamine signaling outside the striatum can alleviate PD.
Movement-related increases in subthalamic activity optimize locomotion
By onWe found most neurons in the STN exhibit increased activity during locomotion. Furthermore, optogenetic inhibition of this activity rapidly dysregulated gait. Thus, the STN facilitates movement and may drive locomotor activity in at-risk DA neurons.
A neurocomputational view of the effects of Parkinson’s disease on speech production
By onThis article reviews the role of cortico-basal ganglia circuits in speech motor learning and execution in Parkinson's disease.
