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Reduced secreted clusterin as a mechanism for Alzheimer-associated CLU mutations Vrije Universiteit Brussel KU Leuven Universiteit Antwerpen
BACKGROUND: The clusterin (CLU) gene has been identified as an important risk locus for Alzheimer's disease (AD). Although the actual risk-increasing polymorphisms at this locus remain to be identified, we previously observed an increased frequency of rare non-synonymous mutations and small insertion-deletions of CLU in AD patients, which specifically clustered in the β-chain domain of CLU. Nonetheless the pathogenic nature of these variants ...
Wnt5a-Induced Wnt1-Inducible Secreted Protein-1 Suppresses Vascular Smooth Muscle Cell Apoptosis Induced by Oxidative Stress KU Leuven
OBJECTIVE: Apoptosis of vascular smooth muscle cells (VSMCs) contributes to thinning and rupture of the atherosclerotic plaque fibrous cap and is thereby associated with myocardial infarction. Wnt protein activation of β-catenin regulates numerous genes that are associated with cell survival. We therefore investigated Wnt/β-catenin survival signaling in VSMCs and assessed the presence of this pathway in human atherosclerotic plaques at various ...
Amyloid Precursor Protein Is Trafficked and Secreted via Synaptic Vesicles KU Leuven
A large body of evidence has implicated amyloid precursor protein (APP) and its proteolytic derivatives as key players in the physiological context of neuronal synaptogenesis and synapse maintenance, as well as in the pathology of Alzheimer's Disease (AD). Although APP processing and release are known to occur in response to neuronal stimulation, the exact mechanism by which APP reaches the neuronal surface is unclear. We now demonstrate that a ...
Secretion and functional display of fusion proteins through the curli biogenesis pathway Vrije Universiteit Brussel
Curli are functional amyloids expressed as fibers on the surface of Enterobacteriaceae. Contrary to the protein misfolding events associated with pathogenic amyloidosis, curli are the result of a dedicated biosynthetic pathway. A specialized transporter in the outer membrane, CsgG, operates in conjunction with the two accessory proteins CsgE and CsgF to secrete curlin subunits to the extracellular surface, where they nucleate into cross-beta ...
Effective Small Molecule Antibacterials from a Novel Anti-Protein Secretion Screen KU Leuven
The increasing problem of bacterial resistance to antibiotics underscores the urgent need for new antibacterials. Protein export pathways are attractive potential targets. The Sec pathway is essential for bacterial viability and includes components that are absent from eukaryotes. Here, we used a new high-throughput videoscreen based on the secretion and activity of alkaline phosphatase(PhoA), a Sec-dependent secreted enzyme that becomes active ...
Understanding the RALF family: a tale of many species Universiteit Gent
Syntenin and syndecan in the biogenesis of exosomes KU Leuven
Cells communicate with their environment in various ways, including by secreting vesicles. Secreted vesicles are loaded with proteins, lipids and RNAs that compose 'a signature' of the cell of origin and potentially can reprogram recipient cells. Secreted vesicles recently gained in interest for medicine. They represent potential sources of biomarkers that can be collected from body fluids and, by disseminating pathogenic proteins, might also ...
ActoBioticsTM voor antigeen-specifieke interventie in type 1 diabetes: mono- of combinatietherapie KU Leuven
In T1D patients, auto-Ags of pancreatic insulin-producing ß-cells are targeted by auto-reactive T cells. The underlying events triggering this excessive auto-reactivity remain unknown, but clearly involve genetic predisposition, allowing inappropriate interaction of environmental factors with the immune system. When diagnosed with T1D, patients are limited to exogenous insulin administrations to control their aberrant glucose metabolism. ...
The genome of Laccaria bicolor provides insights into mycorrhizal symbiosis Universiteit Gent
Mycorrhizal symbioses - the union of roots and soil fungi - are universal in terrestrial ecosystems and may have been fundamental to land colonization by plants(1,2). Boreal, temperate and montane forests all depend on ectomycorrhizae(1). Identification of the primary factors that regulate symbiotic development and metabolic activity will therefore open the door to understanding the role of ectomycorrhizae in plant development and physiology, ...