ADAMs family members as amyloid precursor protein -secretases.

Allinson, Tobias M. J. and Parkin, Edward T. and Turner, Anthony J. and Hooper, Nigel M. (2003) ADAMs family members as amyloid precursor protein -secretases. Journal of Neuroscience Research, 74 (3). pp. 342-352. ISSN 0360-4012

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Abstract

In the non-amyloidogenic pathway, the Alzheimer's amyloid precursor protein (APP) is cleaved within the amyloid- domain by -secretase precluding deposition of intact amyloid- peptide. The large ectodomain released from the cell surface by the action of -secretase has several neuroprotective properties. Studies with protease inhibitors have shown that -secretase is a zinc metalloproteinase, and several members of the adamalysin family of proteins, tumour necrosis factor- convertase (TACE, ADAM17), ADAM10, and ADAM9, all fulfil some of the criteria required of -secretase. We review the evidence for each of these ADAMs acting as the -secretase. What seems to be emerging from numerous studies, including those with mice in which each of the ADAMs has been knocked out, is that there is a team of zinc metalloproteinases able to cleave APP at the -secretase site. We also discuss how upregulation of -secretase activity by muscarinic agonists, cholesterol-lowering drugs, steroid hormones, non-steroidal anti-inflammatory drugs, and metal ions may explain some of the therapeutic actions of these agents in Alzheimer's disease.

Item Type:
Journal Article
Journal or Publication Title:
Journal of Neuroscience Research
Uncontrolled Keywords:
/dk/atira/pure/researchoutput/libraryofcongress/qh301
Subjects:
ID Code:
9463
Deposited By:
Deposited On:
11 Jun 2008 09:28
Refereed?:
Yes
Published?:
Published
Last Modified:
11 Jun 2020 01:36