Mechanisms that prevent Alzheimer's Disease: Enzymatic activity plays key role

Feb 23, 2009

In a project involving the collaboration of several institutes, research scientists of the Johannes Gutenberg University Mainz have succeeded in gaining further insight in the functioning of endogenous mechanisms that protect against the development of Alzheimer's disease. It was found that the activity of the enzyme α-secretase is mainly responsible for the protective effect.

"In the past, we postulated that the enzyme α-secretase was involved in preventing the formation of cerebral plaques characteristic of Alzheimer's disease and also enhanced cerebral functions, such as learning and memory," explained Professor Falk Fahrenholz of the Institute of Biochemistry. His research group has been working in cooperation with the Clinic of Psychiatry and Psychotherapy of the university's Faculty of Medicine and the Central Animal Laboratory Facility (ZVTE) to discover the mechanism for the beneficial effects of α-secretase. The Journal of Alzheimer's Disease (JAD) presents the results of this project in its February 2009 issue.

α-secretase is an endogenous enzyme that is present in the nerve cells of the brain, where it is responsible for the cleavage of an Aβ into Aβ domain. The result is a soluble protein fragment that promotes the growth of nerve cells and thus prevents the development of cerebral deterioration caused by Aβ. However, if the enzyme β-secretase is active, a chain reaction is initiated that subsequently results in the development Aβ initializing the cascade of Alzheimer's disease through formation of Aβ. "You could say that α-secretase is the good enzyme, and β-secretase the bad en-zyme," Fahrenholz commented. "We now want to find out how to activate this 'good' enzyme or increase its concentrations in the brain as a way of combating this disease."

With this in view, the collaborating partners have been investigating whether the positive effects of α-secretase are attributable to its enzymatic activity or whether the protective effect is due to other properties of the enzyme. Enzymes play an important role in the metabolism as they control, regulate and catalyse numerous biochemical processes. "The α-secretase enzyme is a highly complex one, with many other functions. For example, it also relays signals from the intercellular space into cells and interacts with molecules on other cells." Fahrenholz and his colleagues have now established, following investigations in a transgenic mouse model, that it is the enzymatic activity alone that guarantees the protective effects. If this activity is neutralised, the laboratory mice exhibit the symptoms that are characteristic of Alzheimer's disease: impaired learning ability, poor memory capacity and the build-up of Aβ plaques. It is thus possible that the enzymatic activity of α-secretase could represent the starting point for the development of future treatments.

At the same time, the researchers were able to confirm with their experiments that it is not the plaque build-up itself that is responsible for the loss of memory capacity. The cytotoxic substances that accumulate in plaques only destroy neuron synapses when they are still in solution. Prof. Fahrenholz concludes: "It is important to consider other aspects in addition to the plaques themselves, particularly their precursors, which are a real cause of the disease."

More information: Anja Schroeder, Falk Fahrenholz, Ulrich Schmitt, Effect of a dominant-negative form of ADAM10 in a mouse model of Alzheimer's Disease, Journal of Alzheimer's Disease, February 2009, Volume 16:02

Source: IOS Press

Explore further: MSF fighting cholera outbreak in Tanzania refugee camps

Related Stories

Scientists find key to vitamin A metabolism

Dec 10, 2014

Researchers at Case Western Reserve University School of Medicine have uncovered the mechanism that enables the enzyme Lecithin: retinol acyltransferase (LRAT) to store vitamin A—a process that is indispensable ...

The epigenetic switchboard

Jan 12, 2015

Epigenetic signals help determine which genes are activated at which time in a given cell. A novel analytical method enables systematic characterization of the relevant epigenetic tags, and reveals that the ...

'Seeing' hydrogen atoms to unveil enzyme catalysis

Jan 08, 2015

(Phys.org) —Enzymes are catalysts that speed up chemical reactions in living organisms and control many cellular biological processes by converting a molecule, or substrate, into a product used by the cell. ...

Recommended for you

MSF fighting cholera outbreak in Tanzania refugee camps

12 hours ago

Medical charity Medecins sans Frontieres (MSF, Doctors Without Borders) said Sunday it had launched emergency treatment centres in Tanzania, where thousands of Burundians fleeing unrest have been hit by cholera.

Bacteria blamed in indigenous Mexican baby deaths

May 23, 2015

Bacteria—and not a contaminated vaccine as initially suspected—were to blame for the recent deaths of two Mexican babies and for sickening 29 others, according to an official investigation.

Explainer: What is Chagas disease?

May 22, 2015

According to an article in the Journal of the American Medical Association (JAMA), in a Los Angeles clinic treating patients with heart failure, about 20% of Latin American patients have Chagas disease. What is that?, y ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.