A5024914295- MicroRNA in disease regulation
- RNA Research and Splicing
- Neuroscience and Neural Engineering
- RNA modifications and cancer
- Neural dynamics and brain function
- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Genetic Syndromes and Imprinting
- Alzheimer's disease research and treatments
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- Circular RNAs in diseases
- Pluripotent Stem Cells Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related gene regulation
- Neural Networks and Applications
- Nerve injury and regeneration
- Nuclear Structure and Function
- Neurogenetic and Muscular Disorders Research
- Nuclear Receptors and Signaling
- Fibroblast Growth Factor Research
- stochastic dynamics and bifurcation
- Mitochondrial Function and Pathology
Roche (Switzerland)
2022-2025
Roche (Sweden)
2022
Instituto di Biofisica
2016-2021
Scuola Normale Superiore
2016-2021
The Gurdon Institute
2016
Wellcome Trust
2016
A widespread modulation of gene expression occurs in the aging brain, but little is known as to upstream drivers these changes. MicroRNAs emerged fine regulators many biological contexts and they are modulated by age. may therefore be part global correlated with aging-related phenotypes.Here, we show that microRNA-29 (miR-29) induced during short-lived turquoise killifish brain genetic antagonism its function induces a gene-expression signature typical aging. Mechanicistically, identified...
Many RNA-binding proteins (RBPs), particularly those associated with RNA granules, promote pathological protein aggregation in neurodegenerative diseases. Here, we demonstrate that G3BP2, a core component of stress directly interacts Tau and inhibits aggregation. In the human brain, interaction G3BP2 is dramatically increased multiple tauopathies, it independent neurofibrillary tangle (NFT) formation Alzheimer's disease (AD). Surprisingly, pathology significantly elevated upon loss neurons...
ABSTRACT Economic efficiency has been a popular explanation for how networks self-organize within the developing nervous system. However, precise nature of economic negotiations governing this putative organizational principle remains unclear. Here, we address question further by combining large-scale electrophysiological recordings, to characterize functional connectivity neuronal in vitro , with generative modeling approach capable simulating network formation. We find that best fitting...
Studies have provided evidence that human cerebral organoids (hCOs) recapitulate fundamental milestones of early brain development, but many important questions regarding their functionality and electrophysiological properties persist. High-density microelectrode arrays (HD-MEAs) represent an attractive analysis platform to perform functional studies neuronal networks at the cellular network scale. Here, we use HD-MEAs derive large-scale recordings from sliced hCOs. We record activity hCO...
Abstract Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of neuronal E3 ligase UBE3A. Restoring UBE3A levels potential disease-modifying therapy for AS and has recently entered clinical trials. There paucity data regarding molecular changes downstream hampering elucidation disease therapeutics biomarkers. Notably, plays an important role in nucleus but its targets have yet to be elucidated. Using proteomics, we assessed during postnatal cortical development...
Recent research revealed that Tau plays critical roles in various neuronal functions. We previously demonstrated destabilization and nuclear delocalization of alter the expression glutamatergic genes, mediating early damage. In this study, we discovered changes availability are linked to global alterations gene affect multiple pathways. Comparison with human temporal region showed Tau-dependent modulation closely resembles intermediate stages Alzheimer's disease (AD) precede definitive...
Tau is a microtubule-associated protein (MAPT, tau) implicated in the pathogenesis of tauopathies, spectrum neurodegenerative disorders characterized by accumulation hyperphosphorylated, aggregated tau. Because tau pathology can be distinct across diseases, pragmatic therapeutic approach may to intervene at level transcript, as it makes no assumptions mechanisms toxicity. Here we performed large library screen locked-nucleic-acid (LNA)-modified antisense oligonucleotides (ASOs), where...
The capability of generating neural precursor cells with distinct types regional identity in vitro has recently opened new opportunities for cell replacement animal models neurodegenerative diseases. By manipulating Wnt and BMP signaling, we steered the differentiation mouse embryonic stem (ESCs) toward isocortical or hippocampal molecular identity. These two showed different degrees axonal outgrowth targeted regions when co-transplanted healthy lesioned isocortex hippocampus. In...
Antibody libraries are important resources to derive antibodies be used for a wide range of applications, from structural and functional studies intracellular protein interference developing new diagnostics therapeutics. Whatever the goal, key parameter an antibody library is its complexity (also known as diversity), i.e. number distinct elements in collection, which directly reflects probability finding against given antigen, sufficiently high affinity. Quantitative evaluation quality has...
Cerebral cortical development is controlled by key transcription factors that specify the neuronal identities in different layers. The mechanisms controlling their expression distinct cells are only partially known. We investigated and stability of Tbr1, Bcl11b, Fezf2, Satb2, Cux1 mRNAs single developing mouse cells. observe Satb2 mRNA appears much earlier than its protein a set broader expected, suggesting an initial inhibition translation, subsequently released during development....
The morphogen FGF8 plays a pivotal role in neocortical area patterning through its inhibitory effect on COUP-TFI/Nr2f1 anterior expression, but mechanism of action is poorly understood. We established an vitro model mouse embryonic stem cell corticogenesis which COUP-TFI protein expression inhibited by the activation time window corresponding to cortical patterning. Interestingly, overexpression 3′UTR reduces translation. induces few miRNAs targeting silico. found that functional inhibition...
Abstract Iron is an essential metal cofactor for enzymes involved in many cellular functions such as energy generation and cell proliferation. However, excessive iron concentration leads to increased oxidative stress toxicity. As such, homeostasis strictly controlled by two RNA binding proteins known Regulatory Proteins (IRPs) that regulate at post-transcriptional level the expression of management genes. Despite this fine regulation, impairment occurs during aging: progressively accumulates...
Abstract Recent research revealed that Tau plays critical roles in various neuronal functions. Our previous work demonstrated destabilization and nuclear delocalization of can alter the expression glutamatergic genes, thereby mediating early damage. Upon analysing gene coexpression AD temporal regions at different stages transcriptional output differentiated neuroblastoma cells, we discovered changes availability are linked to global alterations affect multiple pathways. Comparison with...
Abstract Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of neuronal E3 ligase UBE3A with no available treatment. Restoring levels via downregulation paternally cis-acting long non-coding antisense transcript (UBE3A-ATS) potential disease modifying. Developing molecules targeting human UBE3A-ATS challenging because it expressed only in neurons and lacks animal species sequence conservation. To overcome this, we performed library screen locked-nucleic acid...
Antibody libraries are important resources to derive antibodies be used for a wide range of applications, from structural and functional studies intracellular protein interference developing new diagnostics therapeutics. Whatever the goal, key parameter an antibody library is its diversity, i.e. number distinct elements in collection, which directly reflects probability finding against given antigen, sufficiently high affinity. Quantitative evaluation diversity quality has been long time...
Withdrawal Statement The authors have withdrawn their manuscript owing to not all having approved the manuscript. Therefore, do wish this work be cited as reference for project. If you any questions, please contact corresponding author.
ABSTRACT Cerebral cortical development is controlled by key transcription factors that specify the neuronal identities in different layers. These are crucial for identity of neurons, but mechanisms controlling their expression distinct cells only partially known. Here we investigate and stability mRNAs Tbr1, Bcl11b, Fezf2, Satb2 Cux1 single developing mouse cells. We focus on find its mRNA occurs much earlier than protein synthesis a set broader expected, suggesting an initially tight...