A5041418069- Alzheimer's disease research and treatments
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- Neuroscience and Neural Engineering
- Advanced Memory and Neural Computing
- Retinal Development and Disorders
- Cholinesterase and Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Fractal and DNA sequence analysis
- Neural dynamics and brain function
- Metabolism and Genetic Disorders
- CRISPR and Genetic Engineering
- Lipid Membrane Structure and Behavior
- Prion Diseases and Protein Misfolding
- Neurobiology and Insect Physiology Research
- Heat shock proteins research
- Parkinson's Disease Mechanisms and Treatments
- Genetics and Neurodevelopmental Disorders
- Machine Learning in Bioinformatics
- Electrochemical Analysis and Applications
- Child Development and Digital Technology
- Plant and Biological Electrophysiology Studies
Vlaams Instituut voor Biotechnologie
2016-2024
Allen Institute for Brain Science
2024
KU Leuven
2011-2024
VIB-KU Leuven Center for Microbiology
2020-2024
VIB-KU Leuven Center for Brain & Disease Research
2011-2022
VIB-KU Leuven Center for Cancer Biology
2012-2014
Tau is a major driver of neurodegeneration and implicated in over 20 diseases. Tauopathies are characterized by synaptic loss neuroinflammation, but it unclear if these pathological events causally linked. binds to Synaptogyrin-3 on vesicles. Here, we interfered with this function determine the role pathogenic at pre-synaptic terminals. We show that heterozygous knockout synaptogyrin-3 benign mice strongly rescues mutant Tau-induced defects long-term plasticity working memory. It also...
Synaptic demise and accumulation of dysfunctional proteins are thought as common features in neurodegeneration. However, the mechanisms by which synaptic turn over remain elusive. In this paper, we study Drosophila melanogaster lacking active TBC1D24/Skywalker (Sky), a protein that humans causes severe neurodegeneration, epilepsy, DOOR (deafness, onychdystrophy, osteodystrophy, mental retardation) syndrome, identify endosome-to-lysosome trafficking mechanism for degradation...
Mitochondria play an important role in the regulation of neurotransmission, and mitochondrial impairment is a key event neurodegeneration. Cells rely on carrier proteins SLC25 family to shuttle ions, cofactors, metabolites necessary for enzymatic reactions. Mutations these carriers often result rare but severe pathologies brain, some genes, including SLC25A39 SLC25A40 , reside susceptibility loci forms epilepsy. However, most has not been investigated neurons vivo . We identified shawn...
Presynaptic terminals can be located far from the neuronal cell body and are thought to independently regulate protein organelle turnover. In this work, we report a soma-centered mechanism that regulates autophagy-driven turnover at distant presynaptic in Drosophila. We show system is regulated by Rab39, whose human homolog mutated Parkinson's disease. Although Rab39 localized soma, its loss of function causes increased autophagy terminals, resulting faster synaptic neurodegeneration. Using...
Event Abstract Back to Increased endosomal microautophagy reduces Tau driven synaptic dysfunction. Valerie Uytterhoeven1*, Liesbeth Deaulmerie1 and Patrik Verstreken1 1 VIB & KU Leuven Center for Brain Disease Research, Belgium Uytterhoeven, Deaulmerie, Verstreken VIB-KU Research 3000, Leuven, Most of the drug discovery efforts in AD have been focused on Aß removal but these studies unsuccessful phase 3 clinical trials. Therefore, there is an urgent need fill therapeutic pipeline with new...
Different pathogenic conditions (Alzheimer's disease and other tauopathies) induce detachment of Tau protein from microtubules. Detached accumulates at synapses binds to synaptic vesicle-associated Synaptogyrin-3, hampering vesicle mobility neurotransmitter release (Zhou et al., Nature Communications 2017). Lowering the levels Synaptogyrin-3 alleviates dysfunction in fruit flies mouse primary neurons McInnes Neuron 2018).We pursued two strategies lower expression a tauopathy model (human...
Event Abstract Back to Tackling Alzheimer’s Disease pathology by modulating the binding of Tau synaptic vesicles Pablo Largo-Barrientos1, 2*, Valerie Uytterhoeven1, 2 and Patrik Verstreken1, 1 KU Leuven, Belgium VIB & Leuven Center for Brain Research, Microtubule-associated protein is implicated in more than 20 neurodegenerative disorders, including Alzheimer's (AD). The association AD was first established after observation neurofibrilarily tangles inside neurons patients' brains which...
Abstract Background We previously identified synaptic vesicle protein Synaptogyrin‐3 as a physical interactor of Tau. Upon mutations and/or hyperphosrylation, Tau accumulates at synapses, binds to and clusters vesicles, reducing mobility neurotransmitter release (McInnes et al., Neuron 2018). Method generated synaptogyrin‐3 knockout mouse usign CRISPR/Cas9. crossed mice with expressing human P301S (PS19 line) generate P301S; +/‐ mice. assessed several aspects mutant Tau‐induced pathology...
Abstract Background Tau tangles are present in the brains of Alzheimer diseased (AD) patients and strategies that remove oligomers tested clinical trials. These anti‐Tau drugs may keep misfolded from spreading damaging additional neurons, but they be inefficient at targeting soluble early disease before formed thus relatively late to spare cognitive defects. Our research is therefore refreshing as it tackle induced dysfunction. We have shown Drosophila overexpression chaperone Hsc70‐4...
Abstract Background Tau is implicated in multiple neurodegenerative disorders, including Alzheimer’s disease. Synaptic loss and neuroinflammation are characteristic feautures of tauopathies, but it unclear if these pathological events causally linked whether they relevant for cognitive decline. Mutations and/or hyperphosphorylation leads its accumulation at synapses, where binds to synaptic vesicle‐associated protein Synaptogyrin‐3 resulting clustering vesicles impaired function. Given that...
Tau's primary localization is in the axons of neurons. At axons, Tau binds microtubuli and stabilizes them. Many pathogenic mutations interfere with binding to resulting relocation different neuronal compartments, including presynapse. Our lab has shown that interact synaptic vesicles via vesicle protein, Synaptogyrin-3 excessive levels at presynapses results sequestration compromising neurotransmission mutant fly mouse neurons (Zhou, Nat. Commun. 2017; McInnes, Neuron, 2018). In addition,...