A5031311373- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Zebrafish Biomedical Research Applications
- Alzheimer's disease research and treatments
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- RNA modifications and cancer
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Tryptophan and brain disorders
- RNA Interference and Gene Delivery
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- RNA and protein synthesis mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Developmental Biology and Gene Regulation
- Cell Image Analysis Techniques
- Nuclear Receptors and Signaling
- Biomedical Text Mining and Ontologies
- Protist diversity and phylogeny
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Genetic and Kidney Cyst Diseases
- Cancer-related molecular mechanisms research
German Center for Neurodegenerative Diseases
2016-2025
Technische Universität Dresden
2015-2025
Izmir Institute of Technology
2017-2018
Human brains are prone to neurodegeneration, given that endogenous neural stem/progenitor cells (NSPCs) fail support neurogenesis. To investigate the molecular programs potentially mediating neurodegeneration-induced NSPC plasticity in regenerating organisms, we generated an Amyloid-β42 (Aβ42)-dependent neurotoxic model adult zebrafish brain through cerebroventricular microinjection of cell-penetrating Aβ42 derivatives. deposits neurons and causes phenotypes reminiscent amyloid...
Abstract Brain activity and connectivity alter drastically during epileptic seizures. The brain networks shift from a balanced resting state to hyperactive hypersynchronous state. It is, however, less clear which mechanisms underlie the transitions. By studying neural glial in zebrafish models of seizures, we observe striking differences between these networks. During preictal period, neurons display small increase synchronous only locally, while gap-junction-coupled network was highly...
The neural stem cell (NSC) reservoir can be harnessed for cell-based regenerative therapies. Zebrafish remarkably regenerate their brain by inducing NSC plasticity in a Amyloid-β-42 (Aβ42)-induced experimental Alzheimer's disease (AD) model. Interleukin-4 (IL-4) is also critical AD-induced proliferation. However, the mechanisms of this response have remained unknown. Using single-cell transcriptomics adult zebrafish brain, we identify distinct subtypes NSCs and neurons differentially...
It was recently suggested that supplying the brain with new neurons could counteract Alzheimer's disease (AD). This provocative idea requires further testing in experimental models which molecular basis of disease-induced neuronal regeneration be investigated. We previously found zebrafish stimulates neural stem cell (NSC) plasticity and neurogenesis AD help to understand mechanisms harnessed for developing diseased mammalian brains. Here, by performing single-cell transcriptomics, we...
Motile cilia defects impair cerebrospinal fluid (CSF) flow and can cause brain spine disorders. The development of ciliated cells, their impact on CSF flow, function in axial morphogenesis are not fully understood. We have characterized motile cells within the zebrafish ventricles. show that ventricles undergo restructuring through development, involving a transition from mono- to multiciliated (MCCs) driven by gmnc. MCCs co-exist with monociliated generate directional patterns. These...
In vertebrates, olfactory receptors localize on multiple cilia elaborated dendritic knobs of sensory neurons (OSNs). Although dysfunction can cause anosmia, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a forkhead domain-containing transcription factor traditionally linked with motile biogenesis, expressed OSNs required for epithelium (OE) formation. keeping immotile nature cilia, we...
Abstract To uncover molecular changes underlying blood-brain-barrier dysfunction in Alzheimer’s disease, we performed single nucleus RNA sequencing 24 disease and control brains focused on vascular astrocyte clusters as main cell types of gliovascular-unit. The majority the transcriptional were pericytes. Of targets predicted to interact with astrocytic ligands, SMAD3 , upregulated pericytes, has highest number ligands including VEGFA downregulated astrocytes. We validated these findings...
Blood-brain barrier (BBB) dysfunction is a key feature of Alzheimer's disease (AD), particularly in individuals carrying the APOE-E4 allele. This worsens neuroinflammation and hinders removal toxic proteins, such as amyloid-beta (Aβ42), from brain. In post-mortem brain tissues animal models, we previously reported that fibronectin accumulates at BBB predominantly carriers. Furthermore, found loss-of-function variant 1 (FN1) gene significantly reduces aggregated levels decreases AD risk among...
Neurogenesis is significantly reduced in Alzheimer's disease (AD) and a potential therapeutic target. Contrary to humans, zebrafish can regenerate its diseased brain, thus ideal for studying neurogenesis. To compare the AD-related molecular pathways between humans zebrafish, we compared single cell or nuclear transcriptomic data from amyloid toxicity model controls (N = 12) with datasets of two human adult brains 10 N 48 (Microglia)), one fetal brain 10). Approximately 95.4% cells...
Neurogenesis, crucial for brain resilience, is reduced in Alzheimer's disease (AD) that induces astroglial reactivity at the expense of pro-neurogenic potential, and restoring neurogenesis could counteract neurodegenerative pathology. However, molecular mechanisms promoting fate despite AD pathology are unknown. In this study, we used APP/PS1dE9 mouse model induced Nerve growth factor receptor (Ngfr) expression hippocampus. Ngfr, which promotes neurogenic astroglia during amyloid...
Alzheimer's disease (AD) is a debilitating neurodegenerative in which accumulation of toxic amyloid-β42 (Aβ42) peptides leads to synaptic degeneration, inflammation, neuronal death, and learning deficits. Humans cannot regenerate lost neurons the case AD part due impaired proliferative capacity neural stem/progenitor cells (NSPCs) reduced neurogenesis. Therefore, efficient regenerative therapies should also enhance proliferation neurogenic NSPCs. Zebrafish (Danio rerio) organism, we can...
Sequential neurogenesis determines the functional properties of habenular neurons.
Epitranscriptomic regulation adds a layer of post-transcriptional control to brain function during development and adulthood. The identification RNA-modifying enzymes has opened the possibility investigating role epitranscriptomic changes play in disease process. NOP2/Sun RNA methyltransferase 2 (NSun2) is one few known brain-enriched methyltransferases able methylate mammalian non-coding RNAs. NSun2 loss due autosomal-recessive mutations been associated with neurological abnormalities...
Abstract Microtubule-associated TAU protein is a pathological hallmark in Alzheimer’s disease (AD), where hyperphosphorylation of generates neurofibrillary tangles. To investigate the effects regenerative adult vertebrate brain system, we generated cre/lox-based transgenic model zebrafish that chronically expresses human P301L , which variant forms tangles mouse models and humans. Interestingly, found although chronic abundant expression starting from early embryonic development led to...
Astrocytes are abundant cell types in the vertebrate central nervous system and can act as neural stem cells specialized niches where they constitutively generate new neurons. Outside niches, however, these glial not neurogenic. Although injuries mammalian lead to profound proliferation of astrocytes, which cluster at lesion site form a gliotic scar, neurogenesis does take place. Therefore, plausible regenerative therapeutic option is coax endogenous reactive astrocytes pre-neurogenic...
Abstract Microproteins, short functional peptides encoded by small genes, are emerging as critical regulators of cellular processes, yet their roles in mitochondrial function and neurodegeneration remain underexplored. In this study, we identify NCBP2-AS2 an evolutionarily conserved microprotein with significant energy metabolism neurogenesis. Using a combination molecular approaches, including CRISPR/Cas9 knockout models, stoichiometric co- immunoprecipitation, advanced imaging techniques,...
Recent findings suggest that reduced neurogenesis could be one of the underlying reasons for exacerbated neuropathology in humans, thus restoring neural stem cell proliferation and help to circumvent some pathological aspects Alzheimer's disease. We recently identified Interleukin-4/STAT6 signaling as a neuron-glia crosstalk mechanism enables glial adult zebrafish brain 3D cultures human astroglia, which manifest neurogenic properties. In this study, by using single sequencing APP/PS1dE9...
Alzheimer's disease (AD) remains a complex challenge characterized by cognitive decline and memory loss. Genetic variations have emerged as crucial players in the etiology of AD, enabling hope for better understanding mechanisms; yet specific mechanism action those genetic variants remain uncertain. Animal models with reminiscent pathology could uncover previously uncharacterized roles these genes. Using CRISPR/Cas9 gene editing, we generated knockout model abca7, orthologous to human ABCA7...
Recent studies point to the existence of poorly characterized small regulatory RNAs generated from mRNAs, rRNAs and tRNAs. To explore subcellular location tRNA-derived RNAs, 0-1 7-8 h Drosophila embryos were fractionated on sucrose density gradients. Analysis 12,553,921 deep-sequencing reads unfractionated has revealed that tRFs, which are detected mainly 5'ends tRNAs, co-sediment with non-polysomal fractions. Interestingly, expression levels a subset tRFs change temporally following...