Abstract
The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally assessed for the first time in order to integrate neurodegeneration within the energetics of the cancer acid–base conceptual frame. At all levels of study (molecular, biochemical, metabolic, and clinical), the intimate nature of both processes appears to consist of opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranging original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows us to propose new avenues of treatment based upon the intracellular and microenvironmental hydrogen ion dynamics regulating and deregulating the biochemistry and metabolism of both cancer and neural cells. Under the same perspective, the etiopathogenesis and special characteristics of multiple sclerosis (MS) is an excellent model for the study of neurodegenerative diseases and, utilizing this pioneering approach, we find that MS appears to be a metabolic disease even before an autoimmune one. Furthermore, within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth. Finally, and for the first time, a new and integrated model of treatment for MS can now be advanced.
Highlights
As a classical approach to disease in general [1], the concept of homeostasis was initially defined as a balanced and healthy physiological state of the cells, tissues, and systems of the organism
The toxicity is principally mediated by excessive Ca2+ entry, primarily through the N-methyl-Daspartate receptors (NMDARs) [237,238], since NMDARs have a much higher permeability for calcium ions compared to other iGluRs [239,240]
This original “both sides ” perspective represents a radical change in other modern approaches to health and disease, departing from some of the more reductionistic concepts regarding the etiopathogenesis and therapeutics of different diseases and degenerative processes
Summary
As a classical approach to disease in general [1], the concept of homeostasis was initially defined as a balanced and healthy physiological state of the cells, tissues, and systems of the organism. The concept of acid–base balance was initially disregarded from belonging to the homeostatic approach [2] These precedents inspired Hans Selye to create his famous General Adaptation Syndrome, a dynamic mixture of homeostasis and allostasis [3]. The new pH-centric anticancer paradigm [4,5] can be applied as an extension of the field of oncology into the field of neurodegeneration This translational and transversal research among vastly separate fields will allow for a better understanding of the intimate nature of the pH-related deregulation of this homeostatic pHrelated approach, showing that cancer and neurodegeneration are two opposed situations on an acid–base and energetic homeostatic spectrum.
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