Hydrogen Ion Dynamics as the Fundamental Link between Neurodegenerative Diseases and Cancer: Its Application to the Therapeutics of Neurodegenerative Diseases with Special Emphasis on 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 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.

Sustainable Release of Propranolol Hydrochloride Laden with Biconjugated-Ufasomes Chitosan Hydrogel Attenuates Cisplatin-Induced Sciatic Nerve Damage in In Vitro/In Vivo Evaluation

“…The radiation-induced neuropathy of the sciatic nerve has reported the presence of tissue apoptosis and confirmed dysregulation of Bcl-2 and Bax expression in sciatic nerve tissue [ 173 , 174 , 175 ]. In addition, the cisplatin-resistant ovarian cancer cell line model also exhibited apoptosis via intrinsic and extrinsic mechanisms incorporating p53 alterations [ 176 ].…”

The Prime and Integral Cause of Cancer in the Post-Warburg Era

“…However, we should now admit that he was very close to it [31]. This is because, as is becoming accepted by different research groups, the prime cause of cancer and/or of cellular malignant transformation is also the main factor working behind the induction of aerobic glycolysis itself, namely, the selective intracellular alkalization of all tumors and leukemias [32]. Furthermore, even the normal functioning of the tricarboxylic cycle (CTC) was shown to be hindered by alkalosis [13].…”

“…Finally, the initial pH-related paradigm has been progressively extended beyond its initial cancer context to the pathogenesis of human neurodegenerative diseases (HNDDs) [28], mainly to the etiopathogenesis and metabolic treatment of multiple sclerosis (MS) [32]. Finally, a Warburg-like effect has been recently blamed for aerobic glycolysis-mediated neuronal degeneration in some cases of spontaneous Alzheimer's disease [86].…”

Investigating the safety of Fampridine in patients with different stages of multiple sclerosis

“…These symptoms may differ signi cantly from patient to patient and over the course of the disease, depending on the site of the effected neuron bers (1)(2)(3). In a neurodegenerative disease such as MS, ion channels play a signi cant role in the pathology of this disease and these channels are highly considered as potential therapeutic targets (4,5).…”