Cell degeneration induced by amyloid-beta peptides: implications for Alzheimer's disease.
Extracellular accumulation of amyloid-beta (Abeta) peptide and death of neurons in brain regions involved in learning and memory, particularly the cortex and the hippocampus, are central features of Alzheimer's disease (AD). Neuronal Ca2+ overload and apoptosis are known to occur in AD. Abeta might play a role in disrupting Ca2+ homeostasis, and this AD-associated amyloidogenic peptide has been reported to induce apoptotic death in cultured cells. However, the specific intracellular signaling pathways by which Abeta triggers cell death are not yet well defined. This article provides evidence for the involvement of mitochondrial dysfunction in Abeta-induced toxicity and for the role of mitochondria in apoptosis triggered by Abeta. In addition, the endoplasmic reticulum (ER) seems to play a role in Abeta-induced apoptotic neuronal death, the ER stress being mediated by the perturbation of ER Ca2+ homeostasis. It is likely that a better understanding of how Abeta induces neuronal apoptosis will lead to the identification of potential molecular targets for the development of therapies for AD.
Pereira
Cláudia
C
Institute of Biochemistry, Faculty of Medicine and Center for Neurosciences and Cellular Biology of Coimbra, University of Coimbra, 3004-504 Coimbra, Portugal. cpereira@cnc.cj.uc.pt
Ferreiro
Elisabete
E
Cardoso
Sandra Morais
SM
de Oliveira
Catarina Resende
CR
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology
D016229:Amyloid beta-Peptides