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Discovery of molecular pathway of Alzheimer's disease reveals new drug targets
Date:11/20/2012

of clusterin activation in the brains of Alzheimer's patients but not in the brains of patients with other forms of dementia.

Dr Richard Killick from King's College London's Institute of Psychiatry said: "This is the first time we've been able to connect the molecular mechanisms behind the formation of amyloid plaques in the brain with the formation of tangles inside the brain cells, two of the defining features of Alzheimer's disease. Our research has given the most detailed picture yet of how the disease progresses and we hope it will offer leads for the development of new treatments."

The signalling pathway that is turned on by clusterin is called DKK1-WNT. It involves interactions between a number of different molecules that could prove to be useful targets for the development of new drugs.

Current treatments for Alzheimer's are focused on alleviating the symptoms and there is no therapy that can prevent the progression of disease.

Professor Simon Lovestone, also from King's College London's Institute of Psychiatry, who led the study, said: "We have shown that we can block the toxic effects of amyloid when we stop this signalling pathway in brain cells grown in the lab. We believe that if we could block its activity in the brains of Alzheimer's patients too, we may have an opportunity to halt the disease in man. Indeed, we have already begun our own drug development programme to do just that and are at the stage where potential compounds are coming back to us for further testing."

The DKK1-WNT pathways has also been implicated in some human cancers and although there is no evidence for a direct link, the findings from this study mean that there could be an opportunity to make advances in Alzheimer's research by capitalising on knowledge that is being gained from cancer research, the authors suggest.

Dr John Williams, Head of Neuroscience and Mental Health at the Wellcome Trust, which helped fund this study,
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Contact: Jen Middleton
j.middleton@wellcome.ac.uk
44-207-611-7262
Wellcome Trust
Source:Eurekalert

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