title: Voltage-dependent anion channel as a resident protein of lipid rafts: post-transductional regulation by estrogens and involvement in neuronal preservation against Alzheimer's disease.
abstract: The voltage-dependent anion channel, VDAC, is present at the neuronal membrane, where it appears to participate, among others, in the extrinsic apoptotic pathway and in the modulation of amyloid-beta induced injury, suggesting the involvement of this channel in Alzheimer's disease (AD) neurotoxicity. VDAC is also highly concentrated in neuronal lipid raft microdomains of different mouse and human cognitive areas, where it has been shown associated with estrogen receptor alpha (ERα), as a part of a `signalosome' that may activate some intracellular signal transduction. At the plasma membrane level, estrogens and antiestrogens (tamoxifen) have been demonstrated to exert rapid antagonist effects on the activation of VDAC, through their distinct effects on the channel post-transductional modulation. Therefore, part of the alternative mechanisms of estrogen related to neuroprotection against amyloid-beta may involve VDAC phosphorylation, in order to maintain the channel in an unactivated (closing) state. Interestingly, VDAC-ERα association has been shown to be disrupted in neuronal lipid rafts of AD brains, in correlation with the aberrant lipid composition observed in these microstructures, suggesting that disturbance of protein interactions may be related to variation in the physico-chemical properties of these microdomains.
authors.affiliation: Department of Physiology, School of Medicine, La Laguna University, Tenerife, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Herrera
authors.forename: Mario
authors.initials: M
authors.lastname: Diaz
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: Hernández-Fernaud
authors.forename: Eduardo
authors.initials: E
authors.lastname: Salido
authors.forename: Rafael
authors.initials: R
authors.lastname: Alonso
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fernández
authors.forename: Araceli
authors.initials: A
authors.lastname: Morales
authors.forename: Raquel
authors.initials: R
authors.lastname: Marin
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D004967:Estrogens / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D050994:Voltage-Dependent Anion Channels; D013629:Tamoxifen