BACE2 can destroy Alzheimer’s Peptide Beta Amyloid

Posted by MullanMichael on September 21, 2012

In a study recently published online in Molecular Neurodegeneration on September 17, Researchers at the Mayo Clinic in Jacksonville, Florida have identified an enzyme known as BACE2 that can destroy beta-amyloid (Aβ) protein. This protein is a fragment of a larger protein called amyloid precursor protein (APP) and is found in plaques in the brains of Alzheimer’s patients, the most common form of dementia.

After testing hundreds of enzymes for their ability to lower Aβ levels, BACE2 was found to be the most efficient, even though it is a close homolog to BACE1, the enzyme that makes the first out of two cuts in the production of beta-amyloid. BACE2 destroys Aβ by cutting it into smaller fragments. Previous research also showed that BACE2 prevents Aβ production by cutting down the middle of the Aβ portion in the APP; this, however, would not be effective in treating Alzheimer’s disease since the process does not happen in the brain. The results of this study also indicate that inhibiting the functions of BACE2 and similar enzymes, due to the usage of certain clinical drugs and various reasons, may increase chances of Alzheimer’s disease.

The research team has received a grant from the National Institutes of Health to further their studies on BACE2. This recent discovery identifies BACE2 as a potential candidate for therapeutic strategies in treating or preventing Alzheimer’s disease. ("Mayo Clinic")

The first NILVAD project meeting took place on 15-16 February in Dublin. The five year project will conduct Phase III clinical trials of the drug Nilvadipine on some 500 people with mild to moderate Alzheimer’s disease in nine European countries. The trials will determine if Nilvadipine can improve memory and functioning, but also slow the rate of progression of Alzheimer’s disease.

The meeting was chaired by Brian Lawlor (Project Coordinator and Professor of Old Age Psychiatry at Trinity College Dublin) and drew 43 delegates from the 17 partners that will work on the project (see below). Attendees discussed all of the administrative and scientific aspects of the study and established key priorities and timelines. The clinical trials will begin in late 2012 at some 20 sites in France, Germany, Greece, Hungary, Ireland, Italy, the Netherlands, Sweden and the UK. Each trial will last for 18 months, with participants receiving treatment or placebo.

Nilvadipine is a calcium channel blocker that has been used for many years to treat hypertension. Laboratory research has shown that it blocks production of the amyloid protein that is thought to be central to the Alzheimer’s disease process. Amyloid is deposited as plaques in the brains of people with Alzheimer’s disease.


Dr. Michael Mullan research on natural compounds - Flavonoids

Posted by MullanMichael on January 16, 2012


A team of researchers at the Roskamp Institute in Sarasota, Florida lead by Drs. Daniel Paris and Michael Mullan have shown that plant pigments known as flavonoids are able to reduce the toxic amyloid peptide that accumulates in Alzheimer's disease. Flavonoids are a family of plant pigments responsible for the color of petals of many plants. it has long been suggested that flavonoids may have potential therapeutic effects. Cell based studies have previously shown that they can exert anti-alergic, anti-inflammatory, anti-microbial, and potentially anti-cancer effects. Flavonoids are taken in quite large amounts by animals and are included in some human diet. The team at the Roskamp Institute are interested in lowering the production of amyloid the Alzheimer peptide associated with the disease. Drs. Paris, Mullan and colleagues have showed that in cell culture flavonoids can lower the production of amyloid. This appears to occur via the inhibition of the enzyme which makes amyloid. This enzyme, called NFkB, is ubiquitously expressed in cells including neurons. The research suggests that some invivo (animal testing) of flavonoids might be the next step to determine whether they have a potential role in treating Alzheimer's.

The Roskamp Institute is a not-for-profit, stand alone, research institute located in Sarasota, Florida. Under the leadership of Drs. Michael Mullan and Fiona Crawford, the institute has focused its activities on developing new treatments for Alzheimer's disease. The paper on flavonoids and Alzheimer's Abeta was published in the Journal of Bioinformation in 2011.

Bioinformation. 2011;6(6):229-36. Epub 2011 Jun 6.
Flavonoids lower Alzheimer's Aβ production via an NF-KB dependent mechanism. Paris D, Mathura V, Ait-Ghezala G, Beaulieu-Abdelahad D, Patel N, Bachmeier C, Mullan M.

Researchers Discover a Control Switch That Serves to Relieve Cellular Stress

A new discovery by University of San Diego researchers could be the key to opening new doors of understanding and treating a number of neurodegenerative disorders such as, Alzheimer’s, Parkinson’s, and ALS, as well as diabetes, cancer and inflammatory disorders. The ramifications are significant and could vastly improve the process of developing new drug therapies to treat these conditions.

Cell death

The normal process when the body undergoes stress is that the endoplasmic reticulum, where all proteins are stored and shaped, experiences a buildup of unfolded or not properly folded proteins. In order to function properly, proteins must be three-dimensional. When there is stress, the protein shaping process is impacted, producing misshapen proteins. The unfolded protein response (UPR), a cellular stress relief mechanism, senses the problem, and begins to correct the cellular process. If not successful, then the UPR sends a signal to the cell to destroy itself.

A new control switch for the unfolded protein response (UPR) 

According to the study published in EMBO Reports by researchers at the University of California, San Diego School of Medicine, two pathways are involved in cell stress response, the UPR and a nonsense-mediated RNA decay pathway (NMD). Dr. Miles, senior author of the paper, said that the two pathways intersect at some point when there is cell stress, indicating that NMD acts to control UPR so that it does not overreact to mild stress.

Diseases such as cancers, diabetes, Parkinson’s and Alzheimer’s are known to cause significant cell stress at a level that typically triggers a self-destruct signal from the UPR. Without a control mechanism, the resulting acceleration of cell death can lead to a rapid deterioration in the health of the patient. According to the researchers, the intersecting NMD is crucial to normalizing the UPR activities, thus protecting the patient from extreme levels of cell death.