Main > NEUROLOGY. > Alzheimer's Disease > Treatment > PhosphoDiEsterase Inhibitors. > PDE4 Inhibitors. > Org.: USA. C (Rolipram/Mice Study) > NPLS Contents

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Antidepressants are also being eyed as potential treatments. For instance, Authors and colleagues have found that rolipram can halt and even reverse deterioration of learning and memory in a mouse model of Alzheimer s.

Rolipram inhibits phosphodiesterase 4 (PDE4), an enzyme that breaks down cyclic adenosine monophosphate (cAMP). cAMP participates in a series of reactions known as the cAMP/PKA/CREB pathway. This pathway is thought to be involved in learning and memory functions, possibly through the formation and maintenance of synapses and growth of neurons. The researchers found that rolipram, by boosting cAMP levels, counteracts the tendency of A42 to suppress this pathway.

Although rolipram has a half-life of just three hours and is rapidly cleared from the body, it has an enduring effect on cognitive function. Mice treated for just three weeks still show memory benefits at least two months later. Authors and his colleagues, who plan to explore just how long the treatment is effective, note that the drug does not alter production or deposition of amyloid-Beta peptide. Instead, they suspect that rolipram s activation of the cAMP/PKA/CREB pathway alters expression of the genes responsible for the architecture of synapses and dendrites.

The researchers believe their results are the first to show that "inhibition of phosphodiesterase activity might effectively counteract learning and memory defects in Alzheimer s disease. ... Rolipram and other PDE4 inhibitors represent a new approach to treatment that appears to make the synapse more robust and resistant to the effects of amyloid-Beta." Rolipram has another appealing characteristic: It works even better in older mice than in young ones. As the researchers point out, "this widens the possible therapeutic window of this class of compounds, not limiting it to the initial phases of the disease."




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