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Títol: Lipid raft ER signalosome malfunctions in menopause in Alzheimer's disease
Autor: Canerina-Amaro, Ana
Hernandez-Abad, Luis G.
Ferrer, Isidro (Ferrer Abizanda)
Quinto-Alemany, David
Mesa-Herrera, Fatima
Ferri, Carla
Puertas-Avendaño, Ricardo A.
Diaz, Mario
Marín, Raquel
Matèria: Malaltia d'Alzheimer
Estrògens
Metabolisme
Alzheimer's disease
Estrogen
Metabolism
Data de publicació: 1-gen-2017
Publicat per: Frontiers in Bioscience
Resum: The increase in the incidence of Alzheimer's disease (AD) in old women may be attributable to estrogen deficiency, and estrogen replacement therapy may be useful in preventing or delaying the onset of this disease. In neuronal membranes, 17b-estradiol interacts with estrogen receptors (mERs) located in lipid raft signalosomes which trigger neuroprotective responses by anchoring to scaffolding caveolin-1 complexed with other proteins. We suggest that mER-signalosome malfunctions in AD and by menopause due to development of aberrations in these microstructures. Here, we report that mER dissociates from a voltage-dependent anion channel (VDAC), and that progressive dephosphorylation of VDAC1 enhances neurotoxicity. mER dissociates from caveolin-1 and other neuroprotective proteins, including insulin-like growth factor 1 receptor beta. Similar signalosome disarrangements are observed in AD patients. Moreover, in AD, lipid rafts exhibit alterations in lipid composition, and these changes cause an increase in liquid-ordered as compared to controls. Together, the data show that AD and menopause lead to disruption in the lipid raft structure, and disfunctioning of ERalpha and other neuroprotectors integrated into these signalosomes.
Nota: Versió postprint del document publicat a: https://doi.org/10.2741/s476
És part de: Frontiers in Bioscience-Scholar Edition, 2017, vol. 9, p. 111-126
URI: https://hdl.handle.net/2445/155521
Recurs relacionat: https://doi.org/10.2741/s476
ISSN: 1945-0516
Apareix en les col·leccions:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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