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Catechol-O-Methyl Transferase Modulates Cognition in Late Life: Evidence and Implications for Cognitive Enhancement

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Abstract:

Aging is associated with deficits in several cognitive domains as well as a decline in brain dopamine activity. Catechol-O-methyl transferase (COMT), an enzyme involved in the degradation of dopamine, is a critical determinant of the availability of this neurotransmitter in the prefrontal cortex. A functional single nucleotide polymorphism in the COMT gene, Val158Met, modulates the activity of this enzyme and affects cognition and the brain regions underlying this function. The effects of COMT Val158Met polymorphism are magnified in the aging brain. Here, we review the evidence supporting a role of COMT genetic variation in cognitive as well as structural and functional brain changes associated with senescence. We will address the potential modulatory role of genetic and non-genetic factors on the neural and cognitive effects of COMT Val158Met in late life. Furthermore, we will discuss the viability of a COMT-targeted treatment for improving cognitive efficiency in aging.

Keywords: ACE Inhibitors; BDNF-Met; COMT; COMT Inhibitors; Catechol-O-methyl transferase; Dopamine transporter; Working memory; aging; catechol-O-methyl transferase inhibitors; cognition; dopamine; functional magnetic resonance imaging; val158Met

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/187152712800672463

Affiliations: Brain Center for Motor and Social Cognition, Istituto Italiano di Tecnologia@UniPR, Via Universita’ 12, Parma, Italy.

Publication date: May 1, 2012

More about this publication?
  • 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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