Kerensa Broersen

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The mechanisms by which mutations in the presenilins (PSEN) or the amyloid precursor protein (APP) genes cause familial Alzheimer disease (FAD) are controversial. FAD mutations increase the release of amyloid β (Aβ)42 relative to Aβ40 by an unknown, possibly gain-of-toxic-function, mechanism. However, many PSEN mutations paradoxically impair γ-secretase and(More)
We provide a validated and rapid protocol for the solubilization of amyloid β-peptide (Aβ). This procedure involves sequential solubilization using structure-breaking organic solvents hexafluoroisopropanol and DMSO followed by column purification. The low solubility and tendency of Aβ to aggregate considerably impede the in vitro handling and biophysical or(More)
BACE1 cleaves the amyloid precursor protein (APP) at the β-cleavage site (Met(671) -Asp(672) ) to initiate the generation of amyloid peptide Aβ. BACE1 is also known to cleave APP at a much less well-characterized β'-cleavage site (Tyr(681) -Glu(682) ). We describe here the identification of a novel APP mutation E682K located at this β'-site in an early(More)
The amyloid peptides Aβ(40) and Aβ(42) of Alzheimer's disease are thought to contribute differentially to the disease process. Although Aβ(42) seems more pathogenic than Aβ(40), the reason for this is not well understood. We show here that small alterations in the Aβ(42):Aβ(40) ratio dramatically affect the biophysical and biological properties of the Aβ(More)
The β-amyloid peptide (Aβ) is directly related to neurotoxicity in Alzheimer disease (AD). The two most abundant alloforms of the peptide co-exist under normal physiological conditions in the brain in an Aβ(42):Aβ(40) ratio of ∼1:9. This ratio is often shifted to a higher percentage of Aβ(42) in brains of patients with familial AD and this has recently been(More)
Inna Kuperstein, Kerensa Broersen, Iryna Benilova, Jef Rozenski, Wim Jonckheere, Maja Debulpaep, Annelies Vandersteen, Ine Segers-Nolten, Kees Van Der Werf, Vinod Subramaniam, Dries Braeken, Geert Callewaert, Carmen Bartic, Rudi D’Hooge, Ivo Cristiano Martins, Frederic Rousseau*, Joost Schymkowitz* and Bart De Strooper* Department for Molecular and(More)
Syntaxin and Munc18 are, in tandem, essential for exocytosis in all eukaryotes. Recently, it was shown that Munc18 inhibition of neuronal syntaxin 1 can be overcome by arachidonic acid, indicating that this common second messenger acts to disrupt the syntaxin-Munc18 interaction. Here, we show that arachidonic acid can stimulate syntaxin 1 alone, indicating(More)
The aggregation and deposition of the amyloid-β peptide (Aβ) in the brain has been linked with neuronal death, which progresses in the diagnostic and pathological signs of Alzheimer’s disease (AD). The transition of an unstructured monomeric peptide into self-assembled and more structured aggregates is the crucial conversion from what appears to be a(More)
Aggregated forms of the amyloid-β peptide are hypothesized to act as the prime toxic agents in Alzheimer disease (AD). The in vivo amyloid-β peptide pool consists of both C- and N-terminally truncated or mutated peptides, and the composition thereof significantly determines AD risk. Other variations, such as biotinylation, are introduced as molecular tools(More)
Alpha-synuclein is a small cytosolic protein involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Recent studies suggested a lipid-related function for this brain-enriched protein. Since the brain carries a high level of docosahexaenoic acid (DHA) and since the extent of alpha-synuclein gene expression increases in(More)