Affiliations: Departamento de Fisiología, Facultad de Medicina, Valencia, Spain | [x] Department of Biochemistry, M.V. Lomonosov Moscow State University, Moscow, Russia | [y] Department of Biomedical Sciences, Ohio University, Athens, OH, USA
Correspondence:
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Corresponding author: Dr. Jose Viña, Departamento de Fisiología, Facultad de Medicina, Avenida Blasco Ibáñez 15, 46010 Valencia, Spain. Tel.: +34 963 864 650; Fax: +34 963 864 642; E-mail: [email protected]
Note: [1] Present address. Universidad Católica de Valencia, Guillem de Castro 94, 46003 Valencia, Spain.
Note: [2] Present address. Department of Neurology, Hospital Clinico Universitario, Avenida Blasco Ibáñez 17, 46010 Valencia, Spain.
Abstract: The role of free radicals in Alzheimer disease pathophysiology has been appreciated for a long time. Originally, radicals were considered as causative of oxidative damage. More recently their role as signalling molecules in this, as well as in other fields of free radical biology, has been underscored. Mitochondria are both generators and targets of radical damage in aging. In this paper we review evidence that radicals generated in mitochondria in the presence of Aβ are signals that trigger both the mitochondrial and the extra-mitochondrial pathways of apoptosis. There are gender specific differences in mitochondrial Aβ toxicity: mitochondria from young (but not from old) females appear to be protected. 17-β Estradiol or phytoestrogens like genistein prevent the formation of oxidants by mitochondria and protect against mitochondrial Aβ toxicity. Experiments reported here indicate that phytoestrogens might have a role in the prevention of Alzheimer's disease.
