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Free Content Editorial [Hot Topic: COMT as a Drug Target for Nervous System Disorders (Guest Editor: Francesco Papaleo)]

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Catechol-O-methyltransferase (COMT) [1] is a key enzyme involved in the methylation of catechol structures, including dopamine, norepinephrine, epinephrine, caffeine, and catechol estrogens. In the last decade, there has been renewed interest in this enzyme because of the findings that implicate it in the development and manifestations of mental illnesses. It is now commonly accepted that COMT’s most crucial effects are centered in the modulation of prefrontal cortex (PFC)-mediated functions. This might be explained by the major determinant role of COMT in PFC dopaminergic signaling, which is critical for modulating higher order cognitive functions, thereby impacting many domains of human behavior, thought and emotion. However, also regions of the nervous system other than the PFC and biological effectors apart from dopamine might be affected by COMT. This possibility is still less explored and will need to be addressed in future studies. Nevertheless, COMT pleiotropic behavioral effects seem consistent and real. In particular, from studies conducted in both mouse models and humans, COMT enzyme activity seems to be involved in an apparent evolutionary trade-off between cognitive and affective functions [2-4]. The knowledge acquired so far, indicate COMT as an attractive drug target potentially having important implications for several disorders of the nervous system. Indeed, as it is evident from the review manuscripts in this special issue, the activity of COMT has been linked to a large spectrum of human phenotypes, including cognition, pain sensitivity, personality, anxiety, psychosis and reward processing. Notably, the level of COMT enzyme activity presents individual changes in the human population because of common functional genetic mutations. Genetic variations in COMT may have important implications in the clinical setting, as changing COMT activity could impact the efficacy and dosing of a particular therapeutic treatment and/or intervention. Therefore, functional genetic variations in COMT are factors that will probably need to be considered in the rational design of more effective and personalized healthcare.....

Document Type: Research Article


Affiliations: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Via Morego 30 16163 Genova Italy.

Publication date: 2012-05-01

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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