CREB and the discovery of cognitive enhancersby

Scott R, Bourtchuladze R,Gossweiler S, Dubnau J, Tully T.

Helen Therapeutics, Inc.,Farmingdale NY 11735, USA.

J Mol Neurosci. 2002 Aug-Oct;19(1-2):171-7

ABSTRACT

In the past few years, a series of molecular-genetic,biochemical, cellular and behavioral studies in fruit flies,sea slugs and mice have confirmed a long-standing notionthat long-term memory formation depends on the synthesisof new proteins. Experiments focused on thecAMP-responsive transcription factor, CREB, haveestablished that neural activity-induced regulation of genetranscription promotes a synaptic growth process thatstrengthens the connections among active neurons. Thisprocess constitutes a physical basis for the engram--andCREB is a "molecular switch" to produce the engram.Helicon Therapeutics has been formed to identify drugcompounds that enhance memory formation viaaugmentation of CREB biochemistry. Candidate compoundshave been identified from a high throughput cell-basedscreen and are being evaluated in animal models ofmemory formation. A gene discovery program also seeks toidentify new genes, which function downstream of CREBduring memory formation, as a source for new drugdiscoveries in the future. Together, these drug and genediscovery efforts promise new class of pharmaceuticaltherapies for the treatment of various forms of cognitivedysfunction.

CREBNew brain cellsFruit-fly memoriesCREBs and memoryThe memory switch?Dumb-drug euphoriaCalcineurin-inhibitionGrowing new brain cellsThe genetics of memoryPhotographic memory in fliesCREB and long-term memoryMemory promoters and suppressorsThe CREB pathway and memory enhancers

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