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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: Article
Journal or Publication Title: Journal of Neuroscience Research
Uncontrolled Keywords: ADAMs • -secretase • cholesterol • non-amyloidogenic • zinc metalloproteinase
Subjects: Q Science > QH Natural history > QH301 Biology
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 9463
Deposited By: Dr Edward Parkin
Deposited On: 11 Jun 2008 10:28
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 18:37
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/9463

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