:
Mental disorders comprise diverse human pathologies including depression, bipolar affective disorder,
schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are unclear
but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in their development
and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of the oxidative hydroxylation
of purines -hypoxanthine and xanthine- to generate uric acid. As a consequence of the oxidative reaction of XO, reactive
oxygen species (ROS) such as superoxide and hydrogen peroxide are produced and, further, contribute to the pathogenesis
of mental disorders. Altered XO activity has been associated with free radical-mediated neurotoxicity inducing cell
damage and inflammation. Diverse studies reported a direct association between an increased activity of XO and diverse
mental diseases including depression or schizophrenia. Small-molecule inhibitors, such as the well-known allopurinol, and
dietary flavonoids, can modulate the XO activity and subsequent ROS production. In the present work, we review the
available literature on XO inhibition by small molecules and their potential therapeutic application in mental disorders. In
addition, we discuss the chemistry and molecular mechanism of XO inhibitors, as well as the use of structure-based and
computational methods to design specific inhibitors with the capability of modulating XO activity.
The Therapy of Aggressivness of Persons with Mental Handicap Combined with Further Mental Diseases
