RSS Feeds

Email a Friend Printer Friendly

Function of key protein in Alzheimer's discovered

August 21, 2003

Scientists at the University of Bonn, working in collaboration with Italian researchers, have discovered the biological function of a protein normally associated with the onset of the Alzheimer's disease. Their results were published at the end of September in the US periodical "FASEB Journal", and the full-length report is already available online (http://www.fasebj.org/express/).

The cerebral cortex of sufferers of Alzheimer's disease is regularly found to contain protein aggregates, known as Alzheimer's plaques, that consist primarily of Abeta peptides. It is thought that the disease is triggered when they destroy brain cells. Abeta is a cleavage product of APP, a larger precursor protein, which has been detected not only in the nerve cells of the cortex but in almost all cell types found in the organism.

Just why the body should create a protein that can trigger one of the most serious brain diseases has been a major mystery. To find some answers, cell biologists Dr. Gregor Kirfel and Professor Dr. Volker Herzog, assisted by their doctoral research student Thomas Quast, have been engaged in a long-term investigation of the normal function of APP. This work has focused on an alternative cleavage product which, due to its solubility, is designated sAPP („soluble APP"). Normally the body breaks down APP in a way that enables sAPP to be released. This process prevents the formation of the "Alzheimer's protein" Abeta. The Bonn researchers, who are collaborating with a laboratory in Italy, have now found out that both APP and sAPP play a central role in the body's vital mechanisms of defence against UV radiation.

Protection against UV rays is essentially achieved in humans by the deposition of the brown/black pigment melanin in the outer layers of skin, the epidermis: the more melanin deposited, the stronger the skin tan and the higher the UV protection. The pigment is produced in a specific type of skin cells called melanocytes and stored by them in little bubbles known as melanosomes. Like tiny railway wagons these melanosomes transport their cargo along molecular tracks to the point where they unload. The "freight stations" are located in close proximity to another type of cell, the keratinocytes: skin cells that absorb the melanin in order to protect their sensitive DNA from the impact of harmful UV radiation. Individuals who are incapable of producing melanin are far more likely to suffer from skin cancers.

The intact APP appears to ensure that the melanin transport in the melanocytes functions properly. With one side it anchors itself to the membrane of a melanosome, and with the other side it connects up with a motor protein, which then pulls the melanin-filled bubble along the molecular tracks to the designated unloading point. The process is stimulated by the soluble form of APP, the sAPP. This indicates that the whole APP protein and its cleavage product sAPP protect our bodies from UV radiation .

"The Abeta peptide might therefore be a pathogenic remnant of a protein otherwise vital to our well-being," speculates Professor Herzog. "In fact APP reveals two extremely different faces: on the one hand, it can prove to be the cause of an highly threatening disease if the Abeta peptide is released; on the other hand, it performs vital functions when it is correctly broken down and the sAPP is released. The melanocytes have shown us its physiological significance."

Bonn, Universitaet