Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

Abstract

Since the 1970s, when ATP was identified as a co-transmitter in sympathetic and parasympathetic nerves, it and its active metabolite adenosine have been considered relevant signaling molecules in biological and pathological processes in the central nervous system (CNS). Meanwhile, inosine, a naturally occurring purine nucleoside formed by adenosine breakdown, was considered an inert adenosine metabolite and remained a neglected actor on the purinergic signaling scene in the CNS. However, this scenario began to change in the 1980s. In the last four decades, an extensive group of shreds of evidence has supported the importance of mediated effects by inosine in the CNS. Also, inosine was identified as a natural trigger of adenosine receptors. This evidence has shed light on the therapeutic potential of inosine on disease processes involved in neurological and psychiatric disorders. Here, we highlight the clinical and preclinical studies investigating the involvement of inosine in chronic pain, schizophrenia, epilepsy, depression, anxiety, and in neural regeneration and neurodegenerative diseases, such as Parkinson and Alzheimer. Thus, we hope that this review will strengthen the knowledge and stimulate more studies about the effects promoted by inosine in neurological and psychiatric disorders.

Keywords: Alzheimer; Parkinson; adenosine; depression; memory; neural regeneration; pain; uric acid.

FIGURE 1

Inosine metabolism and proposed therapeutic properties. ATP, adenosine triphosphate; ADP, adenosine diphosphate; ADA, adenosine deaminase; AMP, adenosine monophosphate; Ca++, calcium; cAMP, cyclic adenosine monophosphate; ENTs, equilibrative nucleoside transporters; K+, potassium; SAH, S-adenosylhomocysteine.