Beta-secretase

2ohk-800

For nearly all the proteins in our body, their final conformation plays a key role in their function; a receptor needs to fold in the correct way so that it can bind the molecule to which it is specific and an enzyme needs to make sure that its active site can accommodate the substrate for the reaction it catalyzes. 

While the folding of these proteins is intrinsically defined by their constituent amino acids, enzymes such as proteases and proteins called chaperones aid in ensuring the correct conformation is reached. Beta-secretase is one of these proteases.

Beta-secretase, also known as BACE1 or memapsin-2 is a protease – an enzyme that cleaves up proteins – that makes specific cuts during the maturation of specific proteins. It predominantly functions in the development of proteins involved in neural function. These include neuregulin, a protein that helps control the formation of myelin sheaths, which insulate nerves and increase the speed of the signals being sent down them.

However, as useful a protein as beta-secretase is, it has a dark side. When beta-secretase does its job too well, it is directly linked to the development of Alzheimer’s:

Beta-secretase cleaves the amyloid-beta precursor protein (APP) into sAPP-beta and CTF beta-99. Upon cleavage of these molecules by either other secretases or by caspases, molecules are generated that are directly linked to the neurodegeneration seen in Alzheimer’s.
Beta-secretase cleaves the amyloid-beta precursor protein (APP) into sAPP-beta and CTF beta-99. Upon cleavage of these molecules by either other secretases or by caspases, molecules are generated that are directly linked to the neurodegeneration seen in Alzheimer’s.

The study of this mechanism set in motion by the beta-secretase cleavage has lead to many advances in the treatment of Alzheimer’s. Currently, there exists a great deal of excitement over the use of passive immunisation, a process in which antibodies generated outside the body are introduced to induce an immune response, against molecules such as the A-beta peptide.

‘Til next time…

Joe

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.