Editing Cholesterol (section)

====Signaling====
{{Main|Cholesterol signaling}}

Cholesterol is also implicated in cell signaling processes, assisting in the formation of [[lipid raft]]s in the [[plasma membrane]], which brings receptor proteins in close proximity with high concentrations of second messenger molecules.<ref name="Incardona_2000">{{cite journal | vauthors = Incardona JP, Eaton S | title = Cholesterol in signal transduction | journal = Current Opinion in Cell Biology | volume = 12 | issue = 2 | pages = 193–203 | date = April 2000 | pmid = 10712926 | doi = 10.1016/S0955-0674(99)00076-9 }}
</ref> In multiple layers, cholesterol and phospholipids, both electrical insulators, can facilitate speed of transmission of electrical impulses along nerve tissue. For many neuron fibers, a [[myelin]] sheath, rich in cholesterol since it is derived from compacted layers of [[Schwann cell]] or oligodendrocyte membranes, provides insulation for more efficient conduction of impulses.<ref name="isbn0-7817-5056-3">{{cite book |vauthors=Pawlina W, Ross MW | chapter = Supporting Cells of the Nervous System | title = Histology: a text and atlas: with correlated cell and molecular biology | edition = 5th | publisher = Lippincott Williams & Wilkins | location = Philadelphia | year = 2006 | pages = 339 | isbn = 978-0-7817-5056-1 }}</ref> [[Demyelination]] (loss of myelin) is believed to be part of the basis for [[multiple sclerosis]].{{cn|date=December 2024}}

Cholesterol binds to and affects the gating of a number of [[ion channel]]s such as the [[nicotinic acetylcholine receptor]], [[GABAA receptor|GABA<sub>A</sub> receptor]], and the [[inward-rectifier potassium channel]].<ref name="LevitanSingh2014">{{cite journal | vauthors = Levitan I, Singh DK, Rosenhouse-Dantsker A | title = Cholesterol binding to ion channels | journal = Frontiers in Physiology | volume = 5 | pages = 65 | year = 2014 | pmid = 24616704 | pmc = 3935357 | doi = 10.3389/fphys.2014.00065 | doi-access = free }}</ref> Cholesterol also activates the [[estrogen-related receptor alpha]] (ERRα), and may be the [[Endogeny (biology)|endogenous]] [[ligand (biochemistry)|ligand]] for the [[receptor (biochemistry)|receptor]].<ref name="WeiSchwaid2016">{{cite journal | vauthors = Wei W, Schwaid AG, Wang X, Wang X, Chen S, Chu Q, Saghatelian A, Wan Y | title = Ligand Activation of ERRα by Cholesterol Mediates Statin and Bisphosphonate Effects | journal = Cell Metabolism | volume = 23 | issue = 3 | pages = 479–491 | date = March 2016 | pmid = 26777690 | pmc = 4785078 | doi = 10.1016/j.cmet.2015.12.010 }}</ref><ref name="Elsevier2017">{{cite book | vauthors = Zuo H, Wan Y | chapter = Nuclear Receptors in Skeletal Homeostasis | veditors = Forrest D, Tsai S |title=Nuclear Receptors in Development and Disease| chapter-url = https://books.google.com/books?id=ZvupDQAAQBAJ&pg=PA88 |year=2017|publisher=Elsevier Science|isbn=978-0-12-802196-5|pages=88 }}</ref> The constitutively active nature of the receptor may be explained by the fact that cholesterol is ubiquitous in the body.<ref name="Elsevier2017" /> Inhibition of ERRα signaling by reduction of cholesterol production has been identified as a key mediator of the effects of [[statin]]s and [[bisphosphonate]]s on [[bone]], [[muscle]], and [[macrophage]]s.<ref name="WeiSchwaid2016" /><ref name="Elsevier2017" /> On the basis of these findings, it has been suggested that the ERRα should be de-orphanized and classified as a receptor for cholesterol.<ref name="WeiSchwaid2016" /><ref name="Elsevier2017" />