[Frontiers in Bioscience E4, 1420-1433, January 1, 2012]

Estrogen receptors in lipid raft signalling complexes for neuroprotection

Raquel Marin1,2,3, Jorge Marrero-Alonso3,4, Cecilia Fernandez1,3, Debora Cury1,3,5, Mario Diaz2,3,4

1Laboratory of Cellular Neurobiology, Department of Physiology, School of Medicine, La Laguna University, Tenerife, Spain,2Institute of Biomedical Technologies, La Laguna University, Tenerife, Spain, 3Canarian Institute of Cancer Research, Tenerife. Spain, 4Department of Animal Biology, Faculty of Biology, La Laguna University, Tenerife, Spain, 5Department of Anatomy, Pathological Anatomy and Histology, School of Medicine, La Laguna University, Tenerife, Spain

TABLE OF CONTENTS

1. Abstract
2. Estrogen actions to preserve the brain
2.1. Diverse roles of estrogens in the brain
2.2. Neuronal classical and alternative mechanisms of estrogen
3. Lipid rafts: keys to signalling platforms in neurons
3.1. Lipid interactions with raft integral proteins
3.2. Estructural proteins of neuronal lipid rafts
3.3. Neurotrophic signalling and neurotransmission in lipid rafts
4. Membrane estrogen receptors within macromolecular platforms involved in neuroprotection
4.1. Molecular components of macrocomplexes interacting with mERs in lipid rafts
4.2. Relevance of mER association with a voltage-dependent anion channel to palliate Abeta-induced toxicity
5. Estrogen signalling pathways against alzheimer's disease neuropathology
5.1. Membrane estrogen strategies to palliate AD parameters of neurotoxicity
5.2. Modulation of pl-VDAC by estradiol and its relevance against Ab-induced cell death
5.3. Antagonist effects of selective estrogen receptor modulators on pl-VDAC regulation
5.4. Disruption of mER signalling complex in lipid rafts of AD brains
6. Perspectives
7. Acknowledgements
8. References

1. ABSTRACT

Estrogens exert a plethora of actions conducted to brain preservation and functioning. Some of these actions are initiated in lipid rafts, which are particular microstructures of the plasma membrane. Preservation of lipid raft structure in neurons is essential for signal transduction against different injuries, such as Alzheimer's disease (AD). These membrane structures appear to be disrupted as this neuropathology evolves, and that may largely contribute to dysfunction of raft resident proteins involved in intracellular signalling. This review includes a survey of some protein interactions that are involved in the structural maintenance and signal transduction mechanisms for neuronal survival against AD. Particularly relevant are the rapid mechanisms developed by estrogen to prevent neuronal death, through membrane estrogen receptors (mER) interactions with a voltage-dependent anion channel (VDAC) and other protein markers within neuronal lipid rafts. These interactions may have important consequences in estrogen mechanisms to achieve neuroprotection against amyloid beta (Abeta-induced toxicity).