IMR Press / FBS / Volume 9 / Issue 1 / DOI: 10.2741/S476

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


Lipid raft ER signalosome malfunctions in menopause and Alzheimer’s disease

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1 Laboratory of Cellular Neurobiology, Department of Basic Medical Sciences, Medicine Section, Faculty of Health Sciences, University of La Laguna, Santa Cruz de Tenerife, Spain
2 Associate Research Unit ULL-CSIC, Membrane Physiology and Biophysics in Neurodegenerative and Cancer Diseases, University of La Laguna, Sta. Cruz de Tenerife, Spain
3 Institute of Neuropathology, Bellvitge University Hospital, University of Barcelona, IDIBELL, CIBERNED, Hospitalet de Llobregat, Barcelona, Spain
4 Laboratory of Membrane Physiology and Biophysics, Department of Animal Biology, Edaphology and Geology, Biology Section, Faculty of Experimental Sciences, University of La Laguna, Sta. Cruz de Tenerife, Spain

*Author to whom correspondence should be addressed.


Front. Biosci. (Schol Ed) 2017, 9(1), 111–126;
Published: 1 January 2017

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, 17β-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.

Lipid Rafts
Alzheimer’s Disease
Estrogen Receptor Alpha
Voltage-dependent Anion Channel
Caveolin 1
Insulin Growth Factor-1 Receptor Beta
Membrane Lipids
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