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Secretase Assays
 | | | Alzheimer's disease (AD) is characterized by a progressive deposition of the 4 kDa b-amyloid peptide (Ab) in senile plaques and accumulation of tau protein as neurofibrillary tangles. In normal healthy individuals, Ab peptides are present only in small quantities as soluble monomers that circulate in cerebrospinal fluid and blood. However, in AD patients, their levels are significantly increased and they begin to accumulate as insoluble, fibrillar plaques. Ab is a 40 to 43 amino acid peptide that originates from the proteolytic cleavage of the amyloid precursor protein (APP). Processing of APP in vivo occurs by two major pathways. Cleavage of APP at the N-terminus of the Ab region by b-secretase and at the C-terminus by g-secretases represents the amyloidogenic pathway for processing of APP. The b-secretase cleaves APP between residues Met671 and Asp672 and yields sAAPb and C99 fragments. The b-secretase has also been identified as an aspartyl protease (BACE or Asp-2) of unusual nature. It has a C-terminal transmembrane domain and two active site motifs located in the luminal domain.
APP can also be processed by a-secretase, which cleaves within the Ab domain between Lys687 and Leu688 and produces a large soluble a-APP domain and the C-terminal fragment containing P3 and C83. The latter can then be cleaved by g-secretase at residue 711 or 713 to release P3 fragment. This pathway does not yield Ab peptide. Hence, shunting APP towards the a-secretase pathway may have a beneficial effect in lowering Ab peptide levels. It is reported that a-secretase shares many of its properties with the secretase that cleaves angiotensin-converting enzyme and is believed to be a zinc metalloproteinase of the ADAMs family (variously ADAM9, ADAM10 and ADAM17/TACE have been implicated). Muscarinic agonists (M1 and M3) and some PKC activators are reported to enhance a-secretase activity and are under consideration for their therapeutic value as AD treatment tools. | | |
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| b-Secretase Activity Assay Kit, Fluorogenic |
Cuvette or 96-well plate |
100 Tests |
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1.5 h |
Cell lysates, tissue extracts, purified BACE |
565785 |
| InnoZyme™ TACE Activity Kit |
96-well plate |
96 Tests |
5-100 ng/ml as measured with purified recombinant human TACE |
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Cells |
CBA042 |
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| | | | Related Resources | | Alzheimer's Disease Related Products: a-Secretase | | Alzheimer's Disease Related Products: b-Secretase | | |
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