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Reversing Alzheimer's gene 'blockade' can restore memory, other cognitive functions
Date:2/29/2012

CAMBRIDGE, Mass. -- MIT neuroscientists have shown that an enzyme overproduced in the brains of Alzheimer's patients creates a blockade that shuts off genes necessary to form new memories. Furthermore, by inhibiting that enzyme in mice, the researchers were able to reverse Alzheimer's symptoms.

The finding suggests that drugs targeting the enzyme, known as HDAC2, could be a promising new approach to treating the disease, which affects 5.4 million Americans. The number of Alzheimer's victims worldwide is expected to double every 20 years, and President Barack Obama recently set a target date of 2025 to find an effective treatment.

Li-Huei Tsai, leader of the research team, says that HDAC2 inhibitors could help achieve that goal, though it would likely take at least 10 years to develop and test such drugs.

"I would really strongly advocate for an active program to develop agents that can contain HDAC2 activity," says Tsai, director of the Picower Institute for Learning and Memory at MIT. "The disease is so devastating and affects so many people, so I would encourage more people to think about this."

Tsai and her colleagues report the findings in the Feb. 29 online edition of Nature. Lead author of the paper is Johannes Grff, a postdoc at the Picower Institute.

Genome modification

Histone deacetylases (HDACs) are a family of 11 enzymes that control gene regulation by modifying histones proteins around which DNA is spooled, forming a structure called chromatin. When HDACs alter a histone through a process called deacetylation, chromatin becomes more tightly packaged, making genes in that region less likely to be expressed.

HDAC inhibitors can reverse this effect, opening up the DNA and allowing it to be transcribed.

In previous studies, Tsai had shown that HDAC2 is a key regulator of learning and memory. In the new study, her team discovered that inhibiting HDAC2 can reverse A
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Contact: David Vaughn, Picower
dmvaughn@mit.edu
617-452-3342
Massachusetts Institute of Technology
Source:Eurekalert

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