Beta-Amyloid

β -amyloid (more precisely, amyloid -beta 40 ( Aβ40 ) and amyloid -beta 42 ( Aβ42 ) ) are called two peptides (APP ) resulting from cutting the amyloid precursor protein with the help of the enzymes beta - and gamma -secretase, but there is still more factors must be present. Beta -amyloid peptides have antimicrobial function. In normal metabolism, these peptides are generated continuously, but do not store away. Aβ40 and Aβ42 are considered neurotoxic, both are found as deposits in the brain and blood vessels of Alzheimer patients and Down syndrome patients. It is believed, therefore, that the prevention of the known as senile plaques deposits would improve the symptoms of these diseases.

In a recent study it was shown that beta -amyloid is deposited even after a severe traumatic brain injury in the brain. Of the deposits, the lesion is, interestingly, not primarily affected, but other areas of the brain, especially the striatum. There are also frequent changes in Alzheimer's disease. However, a connection between a severe head injury and a subsequent dementia has yet to be proven.

Scientific studies have shown that amyloid -beta plays a central role in information processing in the brain. A certain quantity of the protein is necessary for the transmission of information to neurons. Since the current research is mainly aimed to combat Alzheimer's, to develop drugs that break down protein plaques, this new knowledge has to be included.

Conditions for Aβ synthesis

Other factors for the production of Aβ40/42 are genetic predisposition, as

  • Change of APP by mutation of the APP gene ( familial Alzheimer's type 1)
  • Changes in the gene that encodes apolipoprotein E ( familial Alzheimer type 2).
  • Changes in the gamma -secretase in their presenilin subunits (type 3 and 4)
  • Increased production of APP, such as Down syndrome

These rare changes in the genome may be sufficient in itself to give rise to Aβ in sufficient quantities and thus damage.

Furthermore, there are diet-related risk factors such as cholesterol: cholesterol deficiency in form not in vitro beta -amyloid peptides. This may have to do that Aβ production takes place exclusively in so-called lipid rafts of the cell membrane, and that these structures mainly consist of cholesterol.

However, there seems to be other risk factors. Several drugs increase the Aβ42 production to dangerous levels in vitro and in a mouse model. Are suspected of specific inhibitors for cyclooxygenase 2 and certain isoprenoids.

Toxicity

For the mechanism of neurotoxicity of peptides, there are several explanations. On the one hand, the peptides could form ion channels in the cell membrane of neurons. But possibly it is rather small but numerous membrane defects, which are caused by amyloid, and are responsible for the damage.

Amyloid-Precursor-Protein Digital Object Identifier PubMed Central Nature Neuroscience Nature Medicine
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