*Review* **The Biomedical Uses of Inositols: A Nutraceutical Approach to Metabolic Dysfunction in Aging and Neurodegenerative Diseases**

**Antonio J. López-Gambero 1,2, Carlos Sanjuan 3, Pedro Jesús Serrano-Castro 4, Juan Suárez 2,\* and Fernando Rodríguez de Fonseca 2,\***


Received: 22 July 2020; Accepted: 18 August 2020; Published: 20 August 2020

**Abstract:** Inositols are sugar-like compounds that are widely distributed in nature and are a part of membrane molecules, participating as second messengers in several cell-signaling processes. Isolation and characterization of inositol phosphoglycans containing myo- or d-chiro-inositol have been milestones for understanding the physiological regulation of insulin signaling. Other functions of inositols have been derived from the existence of multiple stereoisomers, which may confer antioxidant properties. In the brain, fluctuation of inositols in extracellular and intracellular compartments regulates neuronal and glial activity. Myo-inositol imbalance is observed in psychiatric diseases and its use shows efficacy for treatment of depression, anxiety, and compulsive disorders. Epi- and scyllo-inositol isomers are capable of stabilizing non-toxic forms of β-amyloid proteins, which are characteristic of Alzheimer's disease and cognitive dementia in Down's syndrome, both associated with brain insulin resistance. However, uncertainties of the intrinsic mechanisms of inositols regarding their biology are still unsolved. This work presents a critical review of inositol actions on insulin signaling, oxidative stress, and endothelial dysfunction, and its potential for either preventing or delaying cognitive impairment in aging and neurodegenerative diseases. The biomedical uses of inositols may represent a paradigm in the industrial approach perspective, which has generated growing interest for two decades, accompanied by clinical trials for Alzheimer's disease.

**Keywords:** Alzheimer's disease; psychiatric disease; depression; anxiety; Down's syndrome; inositol; nutraceutical; insulin signaling; antioxidant; aging
