An integral approach to the etiopathogenesis of human neurodegenerative diseases (HNDDs) and cancer. Possible therapeutic consequences within the frame of the trophic factor withdrawal syndrome (TFWS)

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Authors: Salvador Harguindey, Gorka Orive, Ramón Cacabelos, Enrique Meléndez Hevia, Ramón Díaz de Otazu, et al

Published Date October 2008 Volume 2008:4(6) Pages 1073 - 1087

DOI: http://dx.doi.org/10.2147/NDT.S3800

Salvador Harguindey¹, Gorka Orive^2,6, Ramón Cacabelos³, Enrique Meléndez Hevia⁴, Ramón Díaz de Otazu⁵, et al

¹Institute of Clinical Biology and Metabolism, Vitoria, Spain; ²Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of The Basque Country, Vitoria, Spain; ³Department of Clinical Neuroscience, EuroEspes Biomedical Research Center, Bergondo, La Coruña, Spain; ⁴Institute for Cellular Metabolism, Tenerife, Spain; ⁵Department of Pathology, Hospital Txagorritxu, Vitoria, Spain; ⁶Biotechnology Institute (BTI), Vitoria, Spain

Abstract: A novel and integral approach to the understanding of human neurodegenerative diseases (HNDDs) and cancer based upon the disruption of the intracellular dynamics of the hydrogen ion (H+) and its physiopathology, is advanced. From an etiopathological perspective, the activity and/or deficiency of different growth factors (GFs) in these pathologies are studied, and their relationships to intracellular acid-base homeostasis reviewed. Growth and trophic factor withdrawal in HNDDs indicate the need to further investigate the potential utilization of certain GFs in the treatment of Alzheimer disease and other neurodegenerative diseases.  Platelet abnormalities and the therapeutic potential of platelet-derived growth factors in these pathologies, either through platelet transfusions or other clinical methods, are considered. Finally, the etiopathogenic mechanisms of apoptosis and antiapoptosis in HNDDs and cancer are viewed as opposite biochemical and biological disorders of cellular acid-base balance and their secondary effects on intracellular signaling pathways and aberrant cell metabolism are considered in the light of the both the seminal and most recent data available. The “trophic factor withdrawal syndrome” is described for the first time in English-speaking medical literature, as well as a Darwinian-like interpretation of cellular behavior related to specific and nonspecific aspects of cell biology.

Keywords: neurodegenerative diseases and growth factors; Alzheimer’s Disease, human neurodegenerative diseases, cancer, intracellular acid-base homeostasis, apoptosis, antiapoptosis, etiopathogenesis and treatment

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