Hydrogen Ion Dynamics as the Fundamental Link Between Neurodegenerative Diseases and Cancer. Its Application to the Therapeutics of Neurodegenerative Diseases with Special Emphasis in Multiple Sclerosis

Abstract

The pH-related metabolic paradigm has rapidly grown in cancer research and treatment. In this contribution, this recent oncological perspective has been laterally 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 be opposite mechanisms occurring at the far ends of a physiopathological intracellular pH/extracellular pH (pHi/pHe) spectrum. This wide-ranged original approach now permits an increase in our understanding of these opposite processes, cancer and neurodegeneration, and, as a consequence, allows 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) becomes 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. Also within this paradigm, several important aspects of MS, from mitochondrial failure to microbiota functional abnormalities, are analyzed in depth.

Stress-induced reduction of Na + /H + exchanger isoform 1 promotes maladaptation of neuroplasticity and exacerbates depressive behaviors

“…The brain is highly sensitive to shifts in pH due to proteins involved in regulating neuronal excitability, and effective synaptic transmission is critically dependent on appropriate pH levels (10). There is growing evidence that intracellular pH (pHi) changes in the brain are associated with cognitive, emotional, and psychotic behaviors, and a significant decrease in neuronal pHi may be associated with the severity of depression (11)(12)(13). In this way, changes in homeostasis characteristics caused by intracellular acidification may be a key link between external stress and internal dysfunction.…”