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)

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

Figure 1

Relationships among intracellular signaling factors, pH_i, and poptosis. Abbreviations:↑, stimulation;↓, inhibition; ST, somatostatin; SMP-1, tyrosinephospatase; MDR, multiple drug resistance; GFs, growth factors; Cyt C, cytochrome C; NO, nitric oxide; TFWS, Trophic factor withdrawal syndrome. Notes: For further details see Rideout et al 2001; Reed 2002, ; Waldeimer 2003; Waldeimer et al 2004;Broker et al 2005; Harguindey et al 2007.