Beta secretase

Beta secretase
	Existing structural data : see UniProt P56817
Properties of human protein
Mass / length primary structure	456 amino acids
Secondary to quaternary structure	Monomer; single pass type 1 membrane protein
Isoforms	4th
Identifier
Gene names	BACE1 ; ASP2; BACE; FLJ90568; HSPC104; KIAA1149
External IDs	OMIM : 604252 ; UniProt : P56817 ; MGI : 1346542 ;
Enzyme classification
EC, category	3.4.23.46 , aspartyl protease
MEROPS	A01.004
Occurrence
Homology family	Beta secretase
Parent taxon	Euteleostomi
	Orthologue

Beta secretase , also called BACE1 ( β-site of APP cleaving enzyme ) or memapsin-2 , is an enzyme from the protease family . Proteases are proteins that cut other proteins at certain points. This changes or breaks down proteins. Beta secretase is a so-called transmembrane protein , it is located in the membrane of the endoplasmic reticulum (ER) and the Golgi apparatus . Its active center, with which it performs its enzymatic function, is located in the extramembrane domain and contains two aspartate residues. Hence it is called aspartate protease. The active form of beta secretase is believed to be a dimer ; that is, it consists of two sub-units. Beta secretase is involved in the formation of the myelin sheaths of nerve fibers and the development of Alzheimer's disease .

Role in the development of Alzheimer's disease

Scheme of the processing of the amyloid precursor protein.

The generation of the 40 or 42 amino acid long beta-amyloid constitutes two successive enzymatic cleavages in the amyloid precursor protein APP ( amyloid precursor protein advance). The cleavage by beta-secretase in the extracellular part of the APP releases a soluble, extracellular fragment. This is followed by a further cleavage of the APP remaining in the membrane within its transmembrane domain by gamma secretase . This second cleavage releases the intracellular domain of APP and the β-amyloid peptide (see picture).

The alpha-secretase cuts APP closer to the membrane than the beta-secretase and thus removes a portion of the β-amyloid peptide. Therefore, amyloid plaques only form if the first cleavage step is carried out by beta-secretase, but not by alpha-secretase.

So far, there are no known mutations in the gene for beta secretase that trigger the early familial form of Alzheimer's disease - in contrast to presenilin and APP. Nevertheless, it has been shown that the concentration of beta-secretase is increased in Alzheimer's patients. Since it is assumed that an inhibition of beta-secretase leads to a slowing down of Alzheimer's disease, research is being carried out into corresponding beta-secretase-inhibiting drugs ( beta-secretase inhibitors ).

A study of 1,700 Icelandic patients discovered a natural mutation in the BACE1 gene that was associated with the absence of Alzheimer's disease and dementia.

literature

J. Varghese: BACE: Lead Target for Orchestrated Therapy of Alzheimer's Disease. 1st edition. John Wiley & Sons, 2010, ISBN 978-0-470-29342-3

Web links

beta secretase . PDB Molecule of the month

Individual evidence

↑ T. Jonsson, JK Atwal et al .: Alzheimer disease. Mutation in APP protects against Alzheimer's disease . In: Nature Reviews Neurology . tape 8 , no. 9 , August 2, 2012, p. 473 , doi : 10.1038 / nrneurol.2012.158 .

[1] T. Jonsson, JK Atwal et al .: Alzheimer disease. Mutation in APP protects against Alzheimer's disease . In: Nature Reviews Neurology . tape 8 , no. 9 , August 2, 2012, p. 473 , doi : 10.1038 / nrneurol.2012.158 .