Transferrin C2 and Alzheimer's disease: another piece of the puzzle found?
A significant increase in the occurrence of the transferrin C2 genetic subtype has been found in patients with Alzheimer's disease. This variant has previously been linked to diseases thought to be associated with free radical damage. We hypothesize that Alzheimer's disease is caused by free radical damage to membranes of endocytic vesicles due to defective binding of iron and aluminium by Tf C2. The aluminium binds to the membranes, creating pores, while the iron reacts with H2O2 and superoxide radicals produced by activated microglia (brain phagocytes), to produce hydroxyl radicals (oxidative toxins), which attack the fatty acids in the membranes through these pores. In order to treat the disease successfully, it would be necessary to alleviate the multiple deficiencies caused by these toxins by constantly providing the cells with antioxidants and other essential nutrients. In addition, a drug that would stimulate the regrowth of neurons is needed.
Van Rensburg
S J
SJ
Department of Chemical Pathology, Tygerberg Hospital, Cape Town, South Africa.
Carstens
M E
ME
Potocnik
F C
FC
van der Spuy
G
G
van der Walt
B J
BJ
Taljaard
J J
JJ
D000535:Aluminum / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology; D004705:Endocytosis; D005609:Free Radicals; D014644:Genetic Variation; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007107:Immune System / Q000502:physiology; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D017628:Microglia / Q000378:metabolism; D008954:Models, Biological; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000235:genetics* / Q000378:metabolism*
D005609:Free Radicals; D011990:Receptors, Transferrin; D014168:Transferrin; D017665:Hydroxyl Radical; D000535:Aluminum; D007501:Iron