- Suomennosta abstraktista: Tiedetään että alfasekretaasientsyymi pystyy pilkkomaan liukoisen sAPP peptidin siten että ei muodostu A-betaa.
- Alfasekretaasi kuuluu ADAM-perheeseen ja adamalysiinien proteiiniperheeseen, johon kuuluu monta jäsentä kuten TNFalfa-konvertaasi (TACE), ADAM17), ADAM10 ja ADAM9, joista jokainen täyttää joitain kriteereitä alfa-sekretaasifunktiosta.Eläinkokeista on käynyt ilmi, että on olemassa sinkkiproteinaasien tiimi, joka kykenee pilkkomaan APP peptidiä alfasekretaasin pilkkoamiskohdalta.
- Tutkijat pohtivat myös, miten alfasekretaasin aktiivisuuden ylössäätämisellä voidaan selittää joitain terapeuttisia vaikutuksia AD taudissa, joita on saatu seuraavilla lääkkeillä: muskariiniagonisteilla, kolesterolia alentavilla lääkkeillä, steroidihormoneilla, nonsteroidisilla anti-inflammatorisilla lääkkeillä ja metallijoneilla.
http://www.ncbi.nlm.nih.gov/pubmed/14598310
J Neurosci Res. 2003 Nov 1;74(3):342-52. ADAMs family members as amyloid precursor protein alpha-secretases.Allinson TM1, Parkin ET, Turner AJ, Hooper NM. Author information
Abstract
In
the non-amyloidogenic pathway, the Alzheimer's amyloid precursor
protein (APP) is cleaved within the amyloid-beta domain by
alpha-secretase precluding deposition of intact amyloid-beta peptide.
The large ectodomain released from the cell surface by the action of
alpha-secretase has several neuroprotective properties. Studies with
protease inhibitors have shown that alpha-secretase is a zinc
metalloproteinase, and several members of the adamalysin family of
proteins, tumour necrosis factor-alpha convertase (TACE, ADAM17),
ADAM10, and ADAM9, all fulfil some of the criteria required of
alpha-secretase.
We review the evidence for each of these ADAMs acting as the alpha-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 alpha-secretase site.
We also discuss how upregulation of alpha-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.
Copyright 2003 Wiley-Liss, Inc.
We review the evidence for each of these ADAMs acting as the alpha-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 alpha-secretase site.
We also discuss how upregulation of alpha-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.
Copyright 2003 Wiley-Liss, Inc.
- PMID:14598310 [PubMed - indexed for MEDLINE]
- Muistiin 20.4. 2014
Inga kommentarer:
Skicka en kommentar