Publicaties
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Tauopathy in the young autistic brain: novel biomarker and therapeutic target Universiteit Antwerpen
Given our recent discovery of somatic mutations in autism spectrum disorder (ASD)/intellectual disability (ID) genes in postmortem aged Alzheimer's disease brains correlating with increasing tauopathy, it is important to decipher if tauopathy is underlying brain imaging results of atrophy in ASD/ID children. We concentrated on activity-dependent neuroprotective protein (ADNP), a prevalent autism gene. The unique availability of multiple ...
Inhibition of aquaporin 4 decreases amyloid A beta 40 drainage around cerebral vessels Universiteit Antwerpen
Aquaporin-4 (AQP4) is located mainly in the astrocytic end-feet around cerebral blood vessels and regulates ion and water homeostasis in the brain. While deletion of AQP4 is shown to reduce amyloid-beta (A beta) clearance and exacerbate A beta peptide accumulation in plaques and vessels of Alzheimer's disease mouse models, the mechanism and clearing pathways involved are debated. Here, we investigated how inhibiting the function of AQP4 in ...
Sensitivity–specificity of tau and amyloid β positron emission tomography in frontotemporal lobar degeneration Universiteit Antwerpen
Objective To examine associations between tau and amyloid β (Aβ) molecular positron emission tomography (PET) and both Alzheimer‐related pathology and 4‐repeat tau pathology in autopsy‐confirmed frontotemporal lobar degeneration (FTLD). Methods Twenty‐four patients had [18F]‐flortaucipir–PET and died with FTLD (progressive supranuclear palsy [PSP], n = 10; corticobasal degeneration [CBD], n = 10; FTLD‐TDP, n = 3; and Pick disease, n = 1). All ...
The role of intracellular Ca2+ dynamics in autophagy KU Leuven
The ER is the largest organelle found in the cell and acts as the largest Ca2+ store, with a [Ca2+]ER around 500 µM while the [Ca2+]cyt is around 100 nM. Various proteins, including the SERCA pump and the IP3 receptor, regulate the Ca2+ content of the ER. The high [Ca2+]ER is important for the role of Ca2+ as second messenger, but also for the proper functioning of the ER chaperones involved in the folding of newly synthesised proteins and in ...
Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models. KU Leuven
Many mouse models of Alzheimer's disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V ...
Interactions between polyoxometalates and biological systems: from drug design to artificial enzymes KU Leuven
Polyoxometalates have long been studied in a variety of biological applications. Interactions between the highly charged POM molecules and biological molecules frequently occur through hydrogen-bonding and electrostatic interactions. Tellurium-centred Anderson-Evans POMs show exceptional promise as crystallization agents, while acidic and metal-substituted POMs may provide interesting alternatives to enzymes in proteomics applications. While ...
The role of PTB domain containing adaptor proteins on PICALM-mediated APP endocytosis and localization KU Leuven
One hallmark of Alzheimer's disease (AD) is the presence of amyloid plaques, which mainly consist of the amyloid precursor protein (APP) cleavage product amyloid β (Aβ). For cleavage to occur, the APP must be endocytosed from the cell surface. The phosphatidylinositol binding clathrin assembly protein (PICALM) is involved in clathrin-mediated endocytosis and polymorphisms in and near the gene locus were identified as genetic risk factors for AD. ...
Glycation of Plant Proteins: Regulatory Roles and Interplay with Sugar Signalling? KU Leuven
Glycation can be defined as an array of non-enzymatic post-translational modifications of proteins formed by their interaction with reducing carbohydrates and carbonyl products of their degradation. Initial steps of this process rely on reducing sugars and result in the formation of early glycation products-Amadori and Heyns compounds via Schiff base intermediates, whereas their oxidative degradation or reactions of proteins with α-dicarbonyl ...
G(i/o)-Protein Coupled Receptors in the Aging Brain KU Leuven
Cells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety of key physiological functions regulated by GPCRs, these are main targets of existing drugs. During normal aging, alterations in the expression and ...