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: Malaysia reports first Asian death from MERS virus

add to favorites email to friend print save as pdf

Related Stories

Enzyme controls transport of genomic building blocks

Mar 06, 2014

Our DNA and its architecture are duplicated every time our cells divide. Histone proteins are key building blocks of this architecture and contain crucial information that regulates our genes. Danish researchers ...

A promising new system for cheaper drug preparation

Feb 13, 2014

Researchers at the Institute of Chemical Technology (ITQ), a joint centre of the Universitat Politècnica de València and the Spanish National Research Council (CSIC), and the Delft University of Technology (Netherlands) ...

Tiny tweezers allow precision control of enzymes

Jul 03, 2013

Tweezers are a handy instrument when it comes to removing a splinter or plucking an eyebrow. In new research, Hao Yan and his colleagues at Arizona State University's Biodesign Institute describe a pair of ...

How cells optimize the functioning of their power plants

Mar 05, 2013

Mitochondria, which are probably derived from distant bacterial ancestors incorporated into our cells, have their own DNA. However, we know little about how these organelles, which convert oxygen and consumed nutrients into ...

Recommended for you

Malaysia reports first Asian death from MERS virus

2 hours ago

A Malaysian man who went on a pilgrimage to Saudi Arabia has become the first death in Asia from Middle East respiratory syndrome, while the Philippines has isolated a health worker who tested positive for the deadly coronavirus.

Philippines quarantines man over MERS fears

2 hours ago

Philippine health authorities said Wednesday they have quarantined a Filipino who arrived from the Middle East because he tested positive for the deadly MERS virus.

Thyroid disease risk varies among blacks, Asians, and whites

21 hours ago

An analysis that included active military personnel finds that the rate of the thyroid disorder Graves disease is more common among blacks and Asian/Pacific Islanders compared with whites, according to a study in the April ...

User comments : 0

More news stories

HIV+ women respond well to HPV vaccine

HIV-positive women respond well to a vaccine against the human papillomavirus (HPV), even when their immune system is struggling, according to newly published results of an international clinical trial. The study's findings ...