Sheddase

Sheddases, also called shedding enzymes are membrane - enzymes from the class of proteases.

Function

The sheddases are membrane-bound proteases, which can cut the ectodomain of transmembrane proteins in the extracellular region. The preamble of this process is ectodomain shedding ( engl. to shed = " throw "). Become transmembrane antigens cut, one speaks of the antigen shedding.

Family members

The sheddases many members of the ADAM metalloproteases and the β - secretase BACE1 and BACE2 be expected. Specifically, the sheddases ADAM10 and BACE1 are interesting for new therapeutic approaches for the treatment of Alzheimer 's disease. While the α -secretase ADAM10 the amyloid precursor protein (APP) intersect in the desired manner, this is not the case for BACE1. Various BACE1 inhibitors and stimulators ADAM10 are in development.

In oncology is in ADAM10 the reverse path, ie the inhibition of its function sought. So cuts ADAM10 also mediates HER2/neu-Rezeptor of the cell membrane. HER2/neu-Rezeptor the turn is an important target in the therapy of breast cancer with trastuzumab. Also, betacellulin, an epidermal growth factor, is cut by ADAM10. Other molecules which play an important role in proliferation, differentiation, cell adhesion and cell migration of cancer cells, such as Notch, and E-cadherin CD44 will be processed by this sheddase.

ADAM8 is sheddase for CD23 and L -selectin, and plays an important role in allergic inflammation.