8 August 2009

UK research into amyloid beta

The case of amyloid beta and endothelin-converting enzyme-2
Alzheimer's Australia Dementia News: 6 August 2009
The accumulation of a protein called amyloid beta within the brain is thought to be associated with the development of Alzheimer’s disease, so finding out how to control this accumulation is one of the dominant areas in research. One of the ways that amyloid beta is degraded is via the actions of an enzyme (a protein that catalyses, or enables, a reaction) called endothelin-converting enzyme-2. Endothelin-converting enzyme-2 is expressed in brain tissues; it splits ‘big endothelin’ to produce the blood-vessel constrictor endothelin-1.

Dr Palmer and colleagues from the University of Bristol in the United Kingdom examined the expression of endothelin-converting enzyme-2 in brain tissue from people with Alzheimer’s disease, vascular dementia, and controls.

They found abundant endothelin-converting enzyme-2 in both the hippocampus (an area deep in the brain that is often the first to be affected in Alzheimer’s disease) and the neocortex (the part of the brain that is highly evolved in mammals, including humans, and that is thought to be responsible for higher cognitive functions, such as language, learning, memory, and complex thought). Endothelin-converting enzyme-2 was also present in certain astrocytes and microglia (cells that care for nerve cells in the brain), particularly in the brains of people with Alzheimer’s disease.

In another examination the researchers found that the concentrations of endothelinconverting enzyme-2 in messenger RNA were markedly elevated in the brains of people with Alzheimer’s disease but not in the brains of people with vascular dementia. (RNA is similar to DNA. Messenger RNA is one type of RNA; it carries messages from DNA to structures in cells that produce proteins.) In addition, they found that endothelin-converting enzyme-2 protein concentration was significantly elevated in the brains of people with Alzheimer’s disease, but not in those with vascular dementia.

The researchers also conducted experiments in which they exposed a type of cloned stem cell to amyloid beta. Four hours after exposure, they found that the amount of endothelinconverting enzyme-2 in the messenger RNA had decreased, but after 24 hours there was a marked increase.

Dr Palmer and colleagues report that their findings indicate that amyloid beta accumulation in Alzheimer’s disease is unlikely to be caused by endothelin-converting enzyme-2 deficiency. But it is notable that endothelin-converting enzyme-2 expression is increased, which might minimise amyloid beta accumulation.

The researchers suggest that drugs that stop receptors in cells from accepting the bloodvessel constrictor endothelin-1 might be of benefit in the treatment of Alzheimer’s disease.

Reference: Palmer JC, Baig S, Kehoe PG, and Love S. 2009. Endothelin-converting enzyme-2 is increased in Alzheimer’s disease and up-regulated by Aβ. American Journal of Pathology 175:262-270.

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