Files
Document type
ArticleVersion
Accepted versionPublication date
All rights reserved
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/155521
Lipid raft ER signalosome malfunctions in menopause in Alzheimer's disease
Journal Title
Director/Tutor
Journal ISSN
Volume Title
Related resource
Abstract
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.
Subject
Subject (English)
Citation
Citation
CANERINA-AMARO, Ana, et al. Lipid raft ER signalosome malfunctions in menopause in Alzheimer's disease. Frontiers in Bioscience-Scholar Edition. 2017. Vol. 9, num. 111-126. ISSN 1945-0516. [consulted: 13 of June of 2026]. Available at: https://hdl.handle.net/2445/155521