Blocking a key enzyme may help reverse memory loss

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Interfering with the enzyme that blocks communication between brain cells may help reverse Alzheimer's-related memory loss, MIT researchers have found.

The target enzyme, known as HDAC2, turns genes off. It does this by condensing genes so tightly they can't be expressed. For years, investigators unsuccessfully have tried to develop drugs that target this enzyme alone. But most of the new medications also block other members of the HDAC family, resulting in toxic side effects.

The MIT team found a way to precisely target HDAC2, by blocking its interaction with a binding partner called Sp3.

“We think that HDAC2 serves as a master regulator of memory gene expression, and during Alzheimer's disease it's elevated so it causes an epigenetic blockade of the expression of those memory genes,” said Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory and the study's senior author.

Tsai notes that blocking that mechanism could offer a new way to treat memory loss in Alzheimer's patients. Full findings appear in the Aug. 8 edition of Cell Reports.

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