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.

Untargeted Metabolomics Profiling Reveals Beneficial Changes in Milk of Sows Supplemented with Fermented Compound Chinese Medicine Feed Additive

“…Quercetin [ 31 ], pinocembrin [ 32 , 33 ], pogostone [ 34 ], adenosine [ 35 ], ferulic acid [ 36 ], echimidine-N-oxide [ 37 ], purines including adenine, guanine, xanthine and hypoxanthine [ 38 , 39 , 40 ] have strong antibacterial or antifungal effects on diarrheal pathogens, such as Escherichia coli , Salmonella , Staphylococcus aureus , Dysentery bacilli , Pseudomonas aeruginosa , Streptococcus and Clostridioides difficile , in addition, hypoxanthine can speed the excretion of fecal harmful microbiota and toxic substances via shorting gastrointestinal transit time [ 41 ]. Pro-inflammatory substances can also cause diarrhea by impairing the intestinal mucosal barrier with pro-inflammatory cytokines [ 42 ], but quercetin [ 31 ], arteannuin and kynurenine [ 43 , 44 ], ferulic acid [ 45 ], purines [ 46 ], inosine [ 47 , 48 ], guanosine [ 49 ] and benzene-1,2,4-triol [ 50 ] can reduce diarrhea by increasing IFN-γ level or inhibiting the production of pro-inflammatory cytokines [ 48 , 51 , 52 , 53 ]. Supplementation with Perilla frutescens leaf to Holstein cows changed the composition of differential metabolites in the milk and many differential metabolites with antibacterial and anti-inflammatory effects had been identified [ 17 ], results of our experiment also indicated that maternal supplementation with fermented compound Chinese medicine feed additive accumulated lots of high-level differential metabolites in milk which have antibacterial, anti-inflammatory and immune enhancing properties.…”

Harnessing the Therapeutic Potential of the Nrf2/Bach1 Signaling Pathway in Parkinson’s Disease

“…The presumptive neuroprotective action of UA includes scavenging oxygen radicals, chelating iron, blocking iron-dependent oxidation reactions, slowing the DA auto-oxidation rates, stabilizing calcium homeostasis, preserving mitochondrial function, and activating the Nrf2 pathway [ 168 , 169 ]. Various cellular and animal preclinical PD models have shown therapeutic effects of both UA and inosine (reviewed in [ 170 ]) by activating the Nrf2 pathway. However, despite the beneficial effects of inosine and UA in preclinical PD models, a good safety profile in humans, and epidemiological evidence in slowing disease progression in PD, the SURE-PD3 trial was unsuccessful [ 165 ].…”

The Purinergic System as a Target for the Development of Treatments for Bipolar Disorder

“…1a). Inosine can modulate inflammation, neuroprotection, pain, and cognition [34], while UA is associated with sleep, locomotion, cognition, impulsivity, and mood [35][36][37]. Remarkably, this fine-tuning regulation by ectonucleotidases is strictly necessary as both ATP and adenosine can act as neuromodulators and frequently have counteracting effects.…”