Primarily, the cause of Alzheimer's disease is the formation of clumps or plaques of small proteins in the brain. These clumps are clumps are formed from a small protein fragment called Amyloid-beta (A-beta) peptide released from its 'parent' protein - amyloid precursor protein (APP) - a process requiring the action of an enzyme called beta-secetase (BACE), which is critical in clipping up the APP to form the smaller A-beta fragments.

Such is the process that University or Liverpool scientists meant to curb in order to treat Alzheimer's disease by creating a new chemical compound that could later be developed into an anti-Alzheimer's disease drug.

The chemical compound that the research team have used to produce a new compound that can prevent the formation of clumps of small proteins that form in the brain is a family of long chain sugars called Heparan Sulphates (HS).

These HS sugars (found on almost every cell of the body) stick to the BACE enzyme and reduce its ability to 'clip' the A-beta peptide, thereby controlling the amount of A-beta peptide available to form damaging plaques in the brain tissue.

According to Professor Jerry Turnbull from the University of Liverpool's School of Biological Sciences:

"We have developed a new class of compounds called 'engineered heparins' that could possibly be developed into drugs to stop A-beta peptides in the brain from forming and for the first time treat the underlying cause of Alzheimer's. The compound, based on the blood thinning drug, heparin, has modified chemical structures designed to optimise their desired activities and reduce potential side effects.

The compounds work by blocking the beta-secretase enzyme, responsible for snipping proteins into smaller fragments. Despite its central importance to the disease, there are currently no drug treatments which target this enzyme because it has proved difficult to find inhibitors using traditional drug discovery approaches. The new compounds, based on the body's natural substances, may provide a novel route to effective treatments for this debilitating disease."

A company called IntelliHep Ltd, has also been founded to explore the commercial opportunities of developing engineering heparans as new drugs against Alzheimer's and other important medical conditions.

The said research which was funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council is published in the Journal of Medicinal Chemistry.

Source: University of Liverpool

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