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

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.

Relationship of Prevalent Fragility Fracture in Dementia Patients: Three Years Follow up Study

“…Over the last decade, experimental studies, calcium metabolism, and dysregulation of neuronal calcium signalling and alterations in the expression of calcium signalling proteins have been observed in animal models of familial Alzheimer’s disease (AD) [ 43 , 44 , 45 ] and this a possibility of correcting neuronal calcium disruption as a therapeutic approach for AD [ 45 ]. There be could be a role of leptins in osteoporosis [ 46 ], inositols [ 47 ], or Calmodulin [ 48 ] for delaying cognitive impairment, but this needs further research. The current recommendation suggests calcium and vitamin D supplementation in those receiving treatment for osteoporosis and for care home residents who are at high risk of calcium and vitamin D insufficiency [ 49 ].…”

Mutations in the juxtamembrane segment of the cholesterol-binding site of APP alter its processing and promotes production of shorter, less toxic Aβ peptides

“…The present results establish a role of the juxtamembrane region of APP containing the CBS as a regulator of the size of Aβ peptides produced by processing of APP processing: this specific region could then be a novel target for inhibiting cholesterol-binding and reducing the production of toxic Aβ species. K28 has been targeted using lysine-specific molecular tweezers to inhibit assembly and toxicity of amyloid peptides (58–60). It will be of interest to determine whether editing of this residue using CRISPR Cas9, antisense knockdown of the mutant protein, or treatment with antibodies targeting the juxta-membrane region will alter APP processing.…”

Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics

“…Several studies have reported that an antioxidant therapy has beneficial effects in vivo and in vitro animal models for MS. In the context of antioxidant therapy, due to their own antioxidant properties, the use of nutraceutics in neurodegenerative, inflammatory, and metabolic diseases is in constant expansion in order to ameliorate or prevent aging-related diseases [ 113 ]. These molecules are easily extracted from plants or derived from fermentation in bioreactors [ 113 ].…”

“…In the context of antioxidant therapy, due to their own antioxidant properties, the use of nutraceutics in neurodegenerative, inflammatory, and metabolic diseases is in constant expansion in order to ameliorate or prevent aging-related diseases [ 113 ]. These molecules are easily extracted from plants or derived from fermentation in bioreactors [ 113 ]. Among people with MS, nutraceutics are commonly used, often concomitantly with conventional treatment [ 114 ].…”

“…The figure shows the alterations of lymphocytes (blue semicircle) and mitochondrial lymphocytes (red semicircle) observed in MS. cyclic AMP (cAMP) level has been found decrease in peripheral blood mononuclear cells of relapsing remitting (RR) MS patients [ 84 ]. The general observation on T cells is that increasing cAMP levels, by phosphodiesyterase inhibitors (PDEi) [ 74 , 78 , 79 , 80 ] or by nutraceutics interventions [ 113 ], attenuates the T lymphocyte mediated immune response by decreasing the pro-inflammatory cytokines production (e.g., interferon-γ (IFN-γ), tumor necrosis α (TNF-α), and interleukin-1β), T cell proliferation, activation, and migration in central nervous system (CNS) as well as increases their apoptosis. Mitochondrial alterations have been observed in lymphocytes of MS in terms of mitochondrial respiration, coupling, dynamics, structure, biogenesis, and mitochondria-mediated apoptosis.…”