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BACE1 and Presenilin: Two Unusual Aspartyl Proteases Involved in Alzheimer’s DiseaseDominguez D.-I. · Hartmann D. · De Strooper B.
Neuronal Cell Biology and Gene Transfer Laboratory, Department of Human Genetics, KU Leuven and VIB4, Leuven, Belgium Corresponding Author
Molecular Genetics Section, VIB4, Departement Menselijke Erfelijkheid, O. & N.
Herestraat 49, bus 602, BE–3000 Leuven (Belgium)
Tel. +32 16 345878, Fax +32 16 347181
Two enzymatic activities are required to generate the pathogenic β-amyloid (Aβ) peptide that accumulates in the brain of Alzheimer’s disease patients. Both activities are carried out by two unusual aspartyl proteases known as β- and γ-secretase. Their therapeutic inhibition appears, therefore, a promising strategy to treat the disease. Transgenic mouse models in which the genes encoding the secretases have been ablated offer an invaluable tool, on the one hand, to gain more insights into the biological function of these proteases and, on the other hand, to predict the consequences that might be associated with enzyme inhibition in vivo.
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