What does ADAM10 do?

Brain diseases ADAM10 plays a key role in the modulation of the molecular mechanisms responsible for dendritic spine formation, maturation and stabilization and in the regulation of the molecular organization of the glutamatergic synapse.

What does ADAM 10 do?

The metalloproteinase and major amyloid precursor protein (APP) α-secretase candidate ADAM10 is responsible for the shedding of proteins important for brain development, such as cadherins, ephrins, and Notch receptors.

What activates ADAM10?

Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells.

How does gamma secretase work?

With more than 90 known substrates, the γ-secretase complex is considered “the proteasome of the membrane”, with central roles in biology and medicine. The protease carries out hydrolysis within the lipid bilayer to cleave the transmembrane domain of the substrate multiple times before releasing secreted products.

What is an Adam cell in biology?

ADAM1. ADAM1 (fertilin α) is a subunit of an integral sperm membrane heterodimeric glycoprotein called fertilin, which plays an important role in sperm-egg interactions.

What are gamma secretase inhibitors?

γ-Secretase inhibitors (GSI) are a class of small-molecule inhibitors that, as the name implies, prevent the cleavage of γ-secretase substrates. A number of GSIs were developed after γ-secretase was identified as an enzyme responsible for the accumulation of β-amyloid in Alzheimer’s disease (11, 12).

What is ADAM Gene?

An ADAM is a transmembrane protein that contains a disintegrin and metalloprotease domain and, therefore, it potentially has both cell adhesion and protease activities. Currently, the ADAM gene family has 29 members, although the function of most ADAM gene products is unknown.

What is the function of a disintegrin?

Disintegrins work by countering the blood clotting steps, inhibiting the clumping of platelets. They interact with the beta-1 and -3 families of integrins receptors.

Why would a chemical inhibitor of γ secretase be potentially useful for treating Alzheimer’s disease?

Gamma secretase inhibitors (GSIs) have long been investigated for their potential as Alzheimer’s disease (AD) treatments due to their ability to block secretion of amyloid β-peptide, the precursor of amyloid plaques associated with AD.

What do metalloproteinases do?

A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases.

What is Echistatin?

Echistatin is a single-chain polypeptide with a molecular weight of 5400 and a native isoelectric point of 8.3. The most abundant amino acid, cysteine, accounts for 8 of the 49 residues in the protein.

How do gamma secretase inhibitors work?

Gamma secretase inhibitors (GSIs) are a class of drugs that gained attention during the past decade in cancer treatment. The use of GSIs for cancers is primarily based on the premise that GSIs act by inhibiting the cleavage of γ-secretase, which result in blocking Notch 1 signaling [272].

Is adam-10 protein present in human articular cartilage?

“ADAM-10 protein is present in human articular cartilage primarily in the membrane-bound form and is upregulated in osteoarthritis and in response to IL-1alpha in bovine nasal cartilage”. The Journal of Histochemistry and Cytochemistry. 49 (9): 1165–76. doi: 10.1177/002215540104900910.

What does the ADAM10 gene do?

This gene encodes an ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. ADAM10 (EC#: 3.4.24.81) is a sheddase, and has a broad specificity for peptide hydrolysis reactions. ADAM10 cleaves ephrin, within the ephrin/eph complex, formed between two cell surfaces.

What is the active site of ADAM10?

The proposed active site of ADAM10 has been identified by sequence analysis, and is identical to enzymes in the Snake Venom metalloprotein domain family.

How effective are ADAM10 inhibitors in the treatment of HER2 over-expressing cells?

In combination with low doses of herceptin, selective ADAM10 inhibitors decrease proliferation in HER2 over-expressing cell lines while inhibitors, that do not inhibit ADAM10, have no impact.