Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk
Friedrich P.Dr. Thinnes, Max Planck Institut (retired)futhin@t-online.de
Submitted May 29, 2013
I propose a biologically-based hypothesis for the association between skin cancer and reduced Alzheimer disease (AD) risk. [1] Amyloid A-beta peptides, cut from the amyloid precursor protein of neurons, are assumed to induce brain-wide neuronal apoptosis via opening plasma lemma-standing type-1 VDAC channels. This process results in AD whenever critical brain regions are affected. [2-4] Either reaction partner carries one or several GxxxG motifs.
Furthermore, data indicate that amyloid A-beta peptides can be extruded from the brain by ABC transporters at the blood-brain barrier and cancerous transformations accompany changes in the expression level and/or the functionality of multidrug resistance modulators that then disturb chemotherapy. [5] However, enhanced extrusion of apoptogenic amyloid A by raised ABC transporter activities of cancer survivors might diminish or even abolish intra-brain apoptotic effect.
These findings, along with other data [5], may explain why cancer survivors have a lower risk of AD. Finally, the VDAC/amyloid interaction model of AD pathogenesis could explain the reverse relationship of AD and cancer. [5]
1. White RS, Lipton RB, Hall CB, Steinerman JR. Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk. Neurology. 2013 May 15. [Epub ahead of print]
2. Thinnes FP. Amyloid A-beta cut from APP by beta secretase BACE1 and gamma secretase, induces apoptosis via opening type-1 porin/VDAC in cell membranes of hypometabolic cells-A basic model for the induction of apoptosis. Mol Genet Metab 2010; 101:301-303.
3. Thinnes FP. Apoptogenic interactions of plasmalemmal type-1 VDAC and A-beta peptides via GxxxG motifs induce Alzheimer's disease - a basic model of apoptosis.Wien Med Wochenschr 2011; 161:274-276.
4. Mattson MP, Begley JG, Mark RJ, Furukawa K. Abeta 25-35 induces rapid lysis of red blood cells: contrast with Abeta1-42 and examination of underlying mechanisms. Brain Res 1997; 771:147-153.
5. Thinnes FP. New findings concerning vertebrate porin II--on the relevance of glycine motifs of type-1 VDAC. Mol Genet Metab 2013; 108:212-224.
For disclosures, contact the editorial office at journal@neurology.org.
I propose a biologically-based hypothesis for the association between skin cancer and reduced Alzheimer disease (AD) risk. [1] Amyloid A-beta peptides, cut from the amyloid precursor protein of neurons, are assumed to induce brain-wide neuronal apoptosis via opening plasma lemma-standing type-1 VDAC channels. This process results in AD whenever critical brain regions are affected. [2-4] Either reaction partner carries one or several GxxxG motifs. Furthermore, data indicate that amyloid A-beta peptides can be extruded from the brain by ABC transporters at the blood-brain barrier and cancerous transformations accompany changes in the expression level and/or the functionality of multidrug resistance modulators that then disturb chemotherapy. [5] However, enhanced extrusion of apoptogenic amyloid A by raised ABC transporter activities of cancer survivors might diminish or even abolish intra-brain apoptotic effect. These findings, along with other data [5], may explain why cancer survivors have a lower risk of AD. Finally, the VDAC/amyloid interaction model of AD pathogenesis could explain the reverse relationship of AD and cancer. [5]
1. White RS, Lipton RB, Hall CB, Steinerman JR. Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk. Neurology. 2013 May 15. [Epub ahead of print]
2. Thinnes FP. Amyloid A-beta cut from APP by beta secretase BACE1 and gamma secretase, induces apoptosis via opening type-1 porin/VDAC in cell membranes of hypometabolic cells-A basic model for the induction of apoptosis. Mol Genet Metab 2010; 101:301-303.
3. Thinnes FP. Apoptogenic interactions of plasmalemmal type-1 VDAC and A-beta peptides via GxxxG motifs induce Alzheimer's disease - a basic model of apoptosis.Wien Med Wochenschr 2011; 161:274-276.
4. Mattson MP, Begley JG, Mark RJ, Furukawa K. Abeta 25-35 induces rapid lysis of red blood cells: contrast with Abeta1-42 and examination of underlying mechanisms. Brain Res 1997; 771:147-153.
5. Thinnes FP. New findings concerning vertebrate porin II--on the relevance of glycine motifs of type-1 VDAC. Mol Genet Metab 2013; 108:212-224.
For disclosures, contact the editorial office at journal@neurology.org.