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PDE4B demonstrates great promise as a target for regulating cognitive function and fear response

In an advance online publication of Neuropsychopharmacology, a collaboration of scientists produced a strain of knockout mice that had an interesting behavioral phenotype.  The enzyme phosphodiesterase-4B (PDE4B) is present in several areas throughout the body, including the brain. These researchers were able to knockout the PDE4B gene.  The PDE4B-inhibited mice showed increased cognitive function, while also having altered fear memory in comparison to wild type mice. The knockout mice were able to recognize familiar mice more quickly, as well as complete puzzles faster1,2. These mice also exhibited a decrease in fear response, suggesting that PDE4B may play a role in the acquisition and retention of fear-based memories.

Researchers are currently developing a brain-penetrant PDE4B inhibitor to test its effectiveness in decreasing fear response and memory retention in mice2. This protein is so compelling in part because of the current lack of effective drugs for memory and cognitive diseases. The inhibitor, if proven effective, could be a powerful therapeutic in humans for anxiety and memory related diseases, such as post-traumatic stress disorder (PTSD). This research could also point to PDE4B as a target for other drugs for diseases such as Alzheimer’s disease. 


(1)   Mcgirr, Alexander et al. "Specific Inhibition of Phosphodiesterase-4B Results in Anxiolysis and Facilitates Memory Acquisition." Neuropsychopharmacology (2015): doi: 10.1038/npp.2015.240

(2)   University of Leeds. "'Brainy' mice raise hope of better treatments for cognitive disorders." ScienceDaily.  


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