CREB and the discovery of cognitive enhancers.
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 notion that long-term memory formation depends on the synthesis of new proteins. Experiments focused on the cAMP-responsive transcription factor, CREB, have established that neural activity-induced regulation of gene transcription promotes a synaptic growth process that strengthens the connections among active neurons. This process constitutes a physical basis for the engram--and CREB is a "molecular switch" to produce the engram. Helicon Therapeutics has been formed to identify drug compounds that enhance memory formation via augmentation of CREB biochemistry. Candidate compounds have been identified from a high throughput cell-based screen and are being evaluated in animal models of memory formation. A gene discovery program also seeks to identify new genes, which function downstream of CREB during memory formation, as a source for new drug discoveries in the future. Together, these drug and gene discovery efforts promise new class of pharmaceutical therapies for the treatment of various forms of cognitive dysfunction.
Scott
Roderick
R
Helen Therapeutics, Inc., Farmingdale NY 11735, USA.
Bourtchuladze
Rusiko
R
Gossweiler
Scott
S
Dubnau
Josh
J
Tully
Tim
T
D000818:Animals; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology*
D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents