A5014570685- Alzheimer's disease research and treatments
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Prion Diseases and Protein Misfolding
- Glycosylation and Glycoproteins Research
- Calcium signaling and nucleotide metabolism
- Genetics and Neurodevelopmental Disorders
- Wnt/β-catenin signaling in development and cancer
- Cholinesterase and Neurodegenerative Diseases
- Retinal Development and Disorders
- Cell Adhesion Molecules Research
- Photoreceptor and optogenetics research
- Nuclear Receptors and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Signaling Pathways in Disease
- Computational Drug Discovery Methods
- Carbohydrate Chemistry and Synthesis
- Nerve injury and regeneration
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- Biotin and Related Studies
KU Leuven
2015-2025
VIB-KU Leuven Center for Brain & Disease Research
2016-2025
Vlaams Instituut voor Biotechnologie
2003-2021
VIB-KU Leuven Center for Cancer Biology
2006-2016
Center for Human Genetics
2009-2013
University of Antwerp
1988-2012
Institut thématique Génétique, génomique et bioinformatique
2011
VIB-KU Leuven Center for Microbiology
2007
Radboud University Nijmegen
2005
Howard Hughes Medical Institute
1997-1999
The metalloprotease ADAM 10 is an important APP alpha-secretase candidate, but in vivo proof of this lacking. Furthermore, invertebrate models point towards a key role the orthologues Kuzbanian and sup-17 Notch signalling. In mouse, function is, however, currently attributed to 17/TACE, while remains unknown. We have created 10-deficient mice. They die at day 9.5 embryogenesis with multiple defects developing central nervous system, somites, cardiovascular system. situ hybridization revealed...
Mutations in the homologous presenilin 1 (PS1) and 2 (PS2) genes cause most common aggressive form of familial Alzheimer’s disease. Although PS1 function dysfunction have been extensively studied, little is known about PS2 vivo . To delineate relationships activities whether mutations involve gain or loss function, we generated homozygous deficient (−/−) PS1/PS2 double mice. In contrast to −/− mice, mice are viable fertile develop only mild pulmonary fibrosis hemorrhage with age. Absence...
In recent years, Drosophila melanogaster has emerged as a powerful model for neuronal circuit development, pathology, and function. A major impediment to these studies been the lack of genetically encoded, specific, universal, phenotypically neutral marker somatodendritic compartment. We have developed such show that it is effective specific in all populations tested peripheral central nervous system. The marker, which we name DenMark (Dendritic Marker), hybrid protein mouse...
Amyloid β (Aβ) peptides, the primary constituents of senile plaques and a hallmark in Alzheimer's disease pathology, are generated through sequential cleavage amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE1) γ-secretase. The early endosome is thought to represent major compartment for processing; however, mechanisms how BACE1 encounters largely unknown. In contrast internalization, which clathrin-dependent, we demonstrate that sorted endosomes via route controlled...
To better understand intrinsic resistance to immune checkpoint blockade (ICB), we established a comprehensive view of the cellular architecture treatment-naive melanoma ecosystem and studied its evolution under ICB. Using single-cell, spatial multi-omics, showed that tumor microenvironment promotes emergence complex transcriptomic landscape. Melanoma cells harboring mesenchymal-like (MES) state, population known confer targeted therapy, were significantly enriched in early on-treatment...
Abstract Phospholipase D3 (PLD3) polymorphisms are linked to late-onset Alzheimer’s disease (LOAD). Being a lysosomal 5’-3’ exonuclease, its neuronal substrates remained unknown as well how defective nucleotide catabolism connects AD-proteinopathy. We identified mitochondrial DNA (mtDNA) major physiological substrate and show manifest build-up in lysosomes of PLD3-defective cells. mtDNA accretion creates degradative (proteolytic) bottleneck that presents at the ultrastructural level marked...
Abnormal calcium signaling is a central pathological component of Alzheimer's disease (AD). Here, we describe the identification class compounds called ReS19-T, which are able to restore homeostasis in cell-based models tau pathology. Aberrant accumulation leads uncontrolled activation store-operated channels (SOCCs) by remodeling septin filaments at cell cortex. Binding ReS19-T septins restores filament assembly state and restrains entry through SOCCs. In amyloid-β tau-driven mouse disease,...
Mutations of presenilin 1 (PS1) causing Alzheimer's disease selectively increase the secretion amyloidogenic betaA4(1-42), whereas knocking out gene results in decreased production both betaA4(1-40) and (1-42) amyloid peptides (De Strooper et al. 1998). Therefore, PS1 function is closely linked to gamma-secretase processing precursor protein (APP). Given ongoing controversy on subcellular localization PS1, it remains unclear at what level secretory endocytic pathways exerts its activity APP...
The γ‐secretase cleavage is the last step in generation of β‐amyloid peptide (Aβ) from amyloid precursor protein (APP). Aβ precipitates plaques brain Alzheimer's disease patients. fate intracellular APP carboxy‐terminal stub generated together with has been, contrast, only poorly documented. analogies between processing and other transmembrane proteins like SREBP Notch suggests that this fragment could have important signalling functions. We demonstrate here APP‐C59 rapidly degraded...
Here, we report on the identification of nucleolar spindle–associated protein (NuSAP), a novel 55-kD vertebrate with selective expression in proliferating cells. Its mRNA and levels peak at transition G2 to mitosis abruptly decline after cell division. Microscopic analysis both fixed live mammalian cells showed that NuSAP is primarily interphase, localizes prominently central spindle microtubules during mitosis. Direct interaction was demonstrated vitro. Overexpression caused profound...
Presenilin (PSEN) deficiency is accompanied by accumulation of endosomes and autophagosomes, likely caused impaired endo-lysosomal fusion. Recently, Lee et al. (2010. Cell. doi: http://dx.doi.org/10.1016/j.cell.2010.05.008) attributed this phenomenon to PSEN1 enabling the transport mature V0a1 subunits vacuolar ATPase (V-ATPase) lysosomes. In their view, mediates N-glycosylation in endoplasmic reticulum (ER); consequently, PSEN prevents glycosylation, compromising delivery unglycosylated...