The Beta secretase belongs to the protease family. It is involved in the formation of beta amyloid, which takes on important tasks in the transmission of information in the brain. At the same time, beta secretase and beta amyloid play an important role in the development of Alzheimer's disease.
What is Beta Secretase?
Beta secretase belongs to the group of proteases, which split proteins at certain points. It is located in the membrane of the endoplasmic reticulum and the Golgi apparatus. Their active center contains two aspartate residues.
This active center is located in the extra membrane area. Beta secretase is also known as aspartate protease. In its active form, it is a dimer. In addition to beta-secretase, there are also alpha- and gamma-secretase. All three proteases break down the protein APP (amyloid precursor protein). Beta-amyloids are formed during beta and gamma secretase. The exact function of APP is not yet known. However, the amyloids seem to play an important role in transmitting information. What is better known, however, is that beta amyloids play an important role in the development of Alzheimer's disease. They can be deposited in the brain as amyloid plaques.
Function, effect & tasks
The function of beta secretase is to break down the protein APP into beta amyloids. There are two beta-amyloids known as amyloid-beta 40 and amyloid-beta 42. They are created with the help of the two enzymes beta-secretase and gamma-secretase. The beta amyloids have an antimicrobial effect.
At the same time, they are involved in building the myelin sheaths of the nerve fibers. However, the amyloids are also neurotoxic. They form so-called amyloid plaques in the brain, which can lead to Alzheimer's disease. These toxic plaques only arise when the protein APP is first cleaved by beta secretase. When split by alpha secretase, water-soluble proteins are formed that do not form plaques. However, a certain amount of beta-amyloids is necessary for the transmission of information to the neurons. Scientific research has even shown that beta amyloids play a central role in the transmission of information in the brain. The mechanism of the processes is not yet sufficiently known.
Education, occurrence, properties & optimal values
Beta secretase is contained in every body cell as a transmembrane component in the endoplasmic reticulum and the Golgi apparatus. In normal metabolism, it constantly produces beta amyloids by cleaving APP for antimicrobial defense. The beta-amyloids are not deposited there. Most of the protein APP protrudes from the cell. The smaller part is in the cell. It is a so-called transmembrane molecule.
In addition to beta-secretase, alpha-secretase also splits the protein APP into smaller, non-amyloid molecules, which, however, are water-soluble and are not deposited anywhere. In contrast to the beta amyloids, the proteins formed by alpha amyloids have neuroprotective properties. They protect the brain from neurotoxic plaques. When the protein APP is split by beta secretase, a water-soluble part is also split off first. Then, as a second step, the remaining molecule is split by gamma secretase into a beta amyloid and into the intracellular domain of APP.
Diseases & Disorders
The role of beta-secretase in connection with the development of Alzheimer's disease is well known. When the concentration of beta amyloids is increased, they can be deposited as amyloid plaques in the brain. This leads to the death of neurons and thus to atrophy of the brain.
The mechanism by which senile plaques develop is not yet fully understood. Beta-amyloids have important functions in the organism. In particular, they play a central role in information processing. However, when their concentration gets too high, they deposit as plaques between the neurons. There are two competing paths of splitting of the precursor APP. APP is either broken down into water-soluble components by alpha secretase or into beta amyloids by beta and gamma secretase. Both reactions are in balance with each other. If this equilibrium is shifted in favor of the second breakdown path, Alzheimer's disease develops.
Several mutations were discovered to be the cause. However, no mutations that affect beta-secretase play a role. Among other things, a genetically modified APP can increase the risk of Alzheimer's disease. The protein APP is encoded by a gene on chromosome 21. A mutation of this gene can lead to Alzheimer's disease. Down syndrome also has an increased likelihood of developing dementia based on senile plaques. The concentration of the protein APP is increased here because chromosome 21 is present three times. Overall, the cause of the disease is not yet fully understood. In addition to genetic factors, inflammatory processes in the brain, infections with prions, diabetes, high cholesterol levels, trauma and environmental influences are also discussed.
It has been suggested that increased aluminum concentrations in food could cause Alzheimer's. Ultimately, however, the condition for the disease is always the formation of senile amyloid plaques from beta amyloids. Alzheimer's disease is characterized by increasing dementia. Cognitive performance decreases and daily activities become increasingly difficult to cope with.
A curative treatment of the disease has not yet been possible. Only the disease process can be slowed down. Efforts are currently being made to develop so-called beta-secretase inhibitors. These are drugs that are supposed to inhibit the activity of beta secretase in order to stop the disease process in Alzheimer's disease. So far, there are no beta-secretase inhibitors on the market. The corresponding drug development is still at an early stage. According to general estimates, the introduction of a drug against Alzheimer's is expected from 2018 at the earliest.
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