Ricciarelli Roberta, Fedele Ernesto
Department of Experimental Medicine, Section of General Pathology, University of Genoa, Genoa, Italy.
Department of Pharmacy, Section of Pharmacology and Toxicology, Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
Br J Pharmacol. 2015 Oct;172(20):4785-9. doi: 10.1111/bph.13257. Epub 2015 Sep 22.
Cyclic adenosine monophosphate (cAMP) is one of the second messengers critically involved in the molecular mechanisms underlying memory formation. In the CNS, the availability of cAMP is tightly controlled by phosphodiesterase 4 (PDE4), a family of enzymes that degrades the cyclic nucleotide to inactive AMP. Among the different PDE4 isoforms, in the last few years PDE4D has been hogging the limelight due to accumulating evidence for its crucial role in cognitive processes, which makes this enzyme a promising target for therapeutic interventions in a variety of pathological conditions characterized by memory impairment, such as Alzheimer's disease. In this article, we review the role of the cAMP signal transduction pathway in memory formation with a particular focus on the recent progress in PDE4D research.
环磷酸腺苷(cAMP)是关键参与记忆形成分子机制的第二信使之一。在中枢神经系统中,cAMP的可用性受到磷酸二酯酶4(PDE4)的严格控制,PDE4是一类将环核苷酸降解为无活性AMP的酶家族。在不同的PDE4亚型中,近年来PDE4D备受关注,因为越来越多的证据表明其在认知过程中起着关键作用,这使得该酶成为治疗多种以记忆障碍为特征的病理状况(如阿尔茨海默病)的有前景的靶点。在本文中,我们综述了cAMP信号转导通路在记忆形成中的作用,特别关注PDE4D研究的最新进展。