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Alzheimer's memory loss due to gene blockade reversed in mice

05 March 2012

By Maria Botcharova

Appeared in BioNews 647

An enzyme associated with memory loss can be blocked to reverse symptoms of Alzheimer's disease in mice, a study has shown.

The enzyme, called histone deacetylase 2 (HDAC2), is overproduced in people with the disease. The researchers, based at Massachusetts Institute of Technology (MIT), suggest that a drug to inhibit HDAC2 could be developed to help Alzheimer's patients.

HDAC2 affects genes responsible for learning and forming new memories. HDAC2 doesn't directly inhibit the genes, but instead interferes with gene expression epigenetically. It does this by causing the DNA strand to become more tightly wound, effectively hiding sections of DNA from the proteins that read and activate the genes.

'If your memory is everything that you know written in a book, then in order to have access, you have to open the book and to turn the pages', Dr Johannes Graff, the study's lead author, told US News. In Alzheimer's, 'this mechanism actually closes your memory book and makes the pages - the genes - inaccessible'.

Previous research suggests that a major cause of Alzheimer's disease is the formation of protein fragments called beta-amyloids, into solid plaques. These plaques clog up the space between brain cells and stop them functioning correctly.

This is not contradicted by the new findings. Indeed, the team at MIT suggests that beta-amyloids may actually trigger overproduction of HDAC2. However, reducing plaque formation would not reverse symptoms of Alzheimer's after HDAC2 had begun its work.

Although the current research identifies a new target for drug therapy in Alzheimer's disease, it may take a long time before an HDAC2 inhibitor becomes available. 'Clinical trials for a new drug may take as long as five years to begin', said Dr Li-Huei Tsai, the research group's team leader. 'If everything goes well, to become an approved drug would probably take at least ten years'.

Dr Brad Dickerson, associate professor of neurology at Harvard Medical School, who was not involved in the study told US News that 'the leap from animal studies to human clinical trials is a big one and always takes many years'. However, he mentioned that HDAC2 inhibitors are currently under investigation as cancer drugs. Those trials, he said, 'will provide an indication of their side effects and other important information'.

The Alzheimer's Society states that there are currently 750,000 people with Alzheimer's disease in the UK.


02 December 2013 - by Siobhan Chan 
Mice that were conditioned to fear a specific smell passed down this fear to their offspring, suggesting that traumatic events can affect gene expression...
30 September 2013 - by Rhys Baker 
Whether painful memories linger or fade may be down to the expression of a single gene, according to researchers at Massachusetts Institute of Technology (MIT), USA...
02 September 2013 - by Michelle Downes 
Age-related memory loss could be the result of low levels of protein in the brain, according to researchers at Columbia University Medical Center (CUMC)...
20 August 2012 - by Dr Sophie Pryor 
Families with higher levels of a protein linked to inflammation may be at a reduced risk of dementia....
16 July 2012 - by Dr Linda Wijlaars 
A rare genetic mutation, found in about one percent of Icelanders in a recent study, appears to protect against Alzheimer's disease and age-related cognitive decline. It is the first mutation found to act in this way and could be a target for future drug therapy...

20 February 2012 - by Dr Caroline Hirst 
Skin cells from volunteers with Down's syndrome have been turned into brain cells in order to provide a new model for researchers to study Alzheimer's disease...
26 September 2011 - by George Frodsham 
Researchers have identified a strong link between a genetic fault and two common neurological disorders. Two independent studies have found that the mutation is common in patients with amyotrophic lateral sclerosis (ALS) and patients with frontotemporal dementia (FTD), particularly if the disease is familial...
11 April 2011 - by Alison Cranage 
International scientists including researchers at Cardiff University, UK and the University of Pennsylvania, USA have discovered five genetic variations associated with Alzheimer's disease. The findings are published in two papers in the journal Nature Genetics...
07 March 2011 - by Alison Cranage 
Scientists at Northwestern University, Chicago have transformed stem cells into a key type of brain cell that dies early in Alzheimer's disease. Their findings will allow scientists to study what causes the cells to die in Alzheimer's, potentially paving the way for new treatments....

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