Beta-secretase 1
- OMIM: 604 252
- UniProt: P56817
- MGI: 1346542
Also BACE1 ( β -site APP cleaving enzyme of ) or memapsin -2 called beta-secretase, an enzyme from the family of proteases. Proteases are proteins ( proteins ) that cut other proteins at specific locations. Thus proteins are altered or removed. Beta-secretase is known as a transmembrane protein that is localized in the membrane of the endoplasmic reticulum (ER) and the Golgi apparatus. Your active center, with which it carries on its enzymatic function, located in the extramembrane domain and contains two aspartate residues. Therefore they are called aspartic protease. The active form of the beta -secretase is likely a dimer, ie it consists of two subunits. The beta -secretase is involved in the formation of the myelin sheath of nerve fibers and the development of Alzheimer 's disease.
Role in the development of Alzheimer's disease
The generation of 40 and 42 amino acids long beta -amyloid requires two sequential enzymatic cleavages in amyloid Vorläuferpotein APP ( amyloid precursor protein ). The cleavage by the beta -secretase in the extracellular part of APP releases a soluble extracellular fragment. It is followed by a further cleavage of remaining in the membrane APP within its transmembrane domain by the gamma -secretase. This second cleavage, the intracellular domain of APP and β -amyloid peptide are released ( 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. Hence it is only formation of amyloid plaques, when the first division step is carried out by beta- secretase, but not at the alpha -secretase.
So far, no mutations in the gene for the beta -secretase are known to trigger the early familial form of Alzheimer's disease - in contrast to presenilin and APP. Nevertheless, it was demonstrated that the concentration of beta -secretase is increased in Alzheimer patients. Since it is believed that inhibition of beta -secretase results in a slowing of Alzheimer's disease ( beta secretase inhibitors) are being researched corresponding beta -secretase inhibitory drugs.
In a study of 1,700 Icelandic patients a natural mutation in the BACE1 gene was discovered, which was associated with the absence of Alzheimer's and dementia.