Mitochondrial oxidant signalling in Alzheimer's disease.
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 A beta are signals that trigger both the mitochondrial and the extra-mitochondrial pathways of apoptosis. There are gender specific differences in mitochondrial A beta toxicity: mitochondria from young (but not from old) females appear to be protected. 17-beta Estradiol or phytoestrogens like genistein prevent the formation of oxidants by mitochondria and protect against mitochondrial A beta toxicity. Experiments reported here indicate that phytoestrogens might have a role in the prevention of Alzheimer's disease.
Viña
Jose
J
Departamento de Fisiología, Facultad de Medicina, Valencia, Spain. jose.vina@uv.es
Lloret
Ana
A
Vallés
Soraya L
SL
Borrás
Consuelo
C
Badía
Mari-Carmen
MC
Pallardó
Federico V
FV
Sastre
Juan
J
Alonso
Maria-Dolores
MD
D000367:Age Factors; D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D016229:Amyloid beta-Peptides; D005609:Free Radicals; D017382:Reactive Oxygen Species; D004958:Estradiol; D019833:Genistein