Beta - Secretase (BACE1) Knockout Mice

Two beta-secretases termed BACE1 and BACE2 have been shown to generate the Alzheimer's disease Abeta peptides. To examine the physiological roles of BACE1 and to determine whether BACE1 is the major beta-secretase in neurons, Johns Hopkins University researchers have created mice with targeted inactivation of both BACE1 alleles. The secretion of Abeta peptides from neurons is abolished in BACE1-deficient cortical neuronal cultures. While intracelllular beat-carboxy terminal fragments of betaAPP and the corresponding APPsbeta fragments are not generated in BACE-/- neurons, the rate of APPsalpha secretion is increased. These results establish that BACE1 is the principal neuronal protease required to cleave beta-amyloid precursor protein.

Inventor(s): Wong, Philip

Type of Offer: Licensing



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