Alpha secretases

Cleavage of the APP by alpha and beta secretase (s); Functions recognized on the APP protein ( proliferation , Ca regulation etc.) are marked in color

Alpha secretases are a family of proteolytic ( protein degrading) enzymes and thus a subgroup of peptidases or proteases . One of the functions of alpha secretases is the cleavage of the membrane protein APP ( amyloid precursor protein ) in a region that is partly inside and partly on the outside or extracellular side of the membrane and is therefore called the transmembrane region . The cleavage site of APP is as Aβ ( Amyloid β ) because the resulting in the development of Alzheimer involved beta-amyloid peptide arises when there by beta- and gamma-secretase is cleaved. Therefore, the cleavage of APP by alpha secretase prevents the formation of the β-amyloid peptide and thus the development of Alzheimer's. The resulting water-soluble product sAPP ( secreted APP ) or APPsα has neuroprotective (nerve cell protecting) functions. The process of cleavage of the APP by the alpha secretases is known as ectodomain shedding .

Alpha secretases belong to the ADAM protein family ( a disintegrin and metalloprotease domain ). These are expressed on the cell surface and are anchored in the cell membrane. Other members of this family have also been identified as alpha-secretases, including ADAM10 , ADAM17 (also TACE , tumor necrosis factor-α converting enzyme ), ADAM9 and ADAM19 .

The activity of alpha secretases is said to have an influence on the control of learning and memory formation. The release of APPsα has neurotrophic effects that counteract apoptosis and promote the formation of new synapses .

Individual evidence

1. ↑ Science online lexica: Entry on "beta amyloid precursor protein" in the lexicon of neuroscience .
2. ↑ Detlev Ganten, Aloys Greither: Molecular Medicine Basics of Age-Specific Diseases , 2004, Springer-Verlag , ISBN 3540008586 .
3. ↑ Frank Tippmann: Activation of the alpha secretase ADAM10 as a new therapeutic approach for the treatment of Alzheimer's disease. ( Memento of the original from May 17, 2014 in the Internet Archive ) Info: The  archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF) Diss. 2008.
4. ↑ TA Bayer, O. Wirths: Alzheimer's dementia. In: Der Nervenarzt 79, No. 3, 2008, pp. 117–128.