Inosine in Neurodegenerative Diseases: From the Bench to the Bedside

Abstract

Neurodegenerative diseases, such as Alzheimer′s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), currently represent major unmet medical needs. Therefore, novel therapeutic strategies are needed in order to improve patients’ quality of life and prognosis. Since oxidative stress can be strongly involved in neurodegenerative diseases, the potential use of inosine, known for its antioxidant properties, in this context deserves particular attention. The protective action of inosine treatment could be mediated by its metabolite urate. Here, we review the current preclinical and clinical studies investigating the use of inosine in AD, PD, ALS, and MS. The most important properties of inosine seem to be its antioxidant action and its ability to raise urate levels and to increase energetic resources by improving ATP availability. Inosine appears to be generally safe and well tolerated; however, the possible formation of kidney stones should be monitored, and data on its effectiveness should be further explored since, so far, they have been controversial. Overall, inosine could be a promising potential strategy in the management of neurodegenerative diseases, and additional studies are needed in order to further investigate its safety and efficacy and its use as a complementary therapy along with other approved drugs.

RFW captures species-level full profile of metagenomic functions via integrating genome annotation information

“…Specially, Oxaloacetic acid can stimulate neurogenesis and activate brain mitochondrial biogenesis [74] . Inosine (Supplementary Figure 7C) was thought to be a potential strategy of neurodegenerative diseases treatment [75,76] . S-Adenosyl-Lhomocysteine(Supplementary Figure 7D) were significantly increased in ASD [77] and this metabolite can be quickly linked to the glutamic acid-homocysteine metabolic network in Figure 6a as L-homocysteine is the precursor of S-Adenosyl-Lhomocysteine.…”

Uric acid and neurological disease: a narrative review

“…However, they also suggested that phase III trials with a longer follow-up period, of more than 1 year, may be needed to evaluate the efficacy of inosine in preventing disease recurrence and progression ( 62 ). Given the results of preclinical and clinical studies of inosine use, the most important properties of inosine seem to be its antioxidant actions and its potential to increase energy resources by improving adenosine triphosphate availability ( 63 ). Table 5 summarized the evidence of investigating the relationship between multiple sclerosis and serum uric acid levels ( 40 – 42 , 51 , 52 , 56 ).…”

New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022

“…Urate, the metabolite of inosine, is an endogenous antioxidant and potential neuroprotectant. Its level is lower in patients with ALS, and a high urate level is associated with improved survival ( Basile et al, 2022 ). Furthermore, increased inosine metabolism may be protective in ALS.…”