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2018-11-28Zeitschriftenartikel DOI: 10.3389/fphar.2018.01369
β-Arrestin Based Receptor Signaling Paradigms: Potential Therapeutic Targets for Complex Age-Related Disorders
dc.contributor.authorvan Gastel, Jaana
dc.contributor.authorHendrickx, Jhana
dc.contributor.authorLeysen, Hanne
dc.contributor.authorSantos-Otte, Paula
dc.contributor.authorLuttrell, Louis
dc.contributor.authorMartin, Bronwen
dc.contributor.authorMaudsley, Stuart
dc.date.accessioned2019-12-19T12:31:55Z
dc.date.available2019-12-19T12:31:55Z
dc.date.issued2018-11-28none
dc.date.updated2019-10-15T08:12:23Z
dc.identifier.urihttp://edoc.hu-berlin.de/18452/21727
dc.description.abstractG protein coupled receptors (GPCRs) were first characterized as signal transducers that elicit downstream effects through modulation of guanine (G) nucleotide-binding proteins. The pharmacotherapeutic exploitation of this signaling paradigm has created a drug-based field covering nearly 50% of the current pharmacopeia. Since the groundbreaking discoveries of the late 1990s to the present day, it is now clear however that GPCRs can also generate productive signaling cascades through the modulation of β-arrestin functionality. β-Arrestins were first thought to only regulate receptor desensitization and internalization – exemplified by the action of visual arrestin with respect to rhodopsin desensitization. Nearly 20 years ago, it was found that rather than controlling GPCR signal termination, productive β-arrestin dependent GPCR signaling paradigms were highly dependent on multi-protein complex formation and generated long-lasting cellular effects, in contrast to G protein signaling which is transient and functions through soluble second messenger systems. β-Arrestin signaling was then first shown to activate mitogen activated protein kinase signaling in a G protein-independent manner and eventually initiate protein transcription – thus controlling expression patterns of downstream proteins. While the possibility of developing β-arrestin biased or functionally selective ligands is now being investigated, no additional research has been performed on its possible contextual specificity in treating age-related disorders. The ability of β-arrestin-dependent signaling to control complex and multidimensional protein expression patterns makes this therapeutic strategy feasible, as treating complex age-related disorders will likely require therapeutics that can exert network-level efficacy profiles. It is our understanding that therapeutically targeting G protein-independent effectors such as β-arrestin will aid in the development of precision medicines with tailored efficacy profiles for disease/age-specific contextualities.eng
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectβ-arrestin signalingeng
dc.subjectligand ‘bias’eng
dc.subjectGPCRseng
dc.subjectage-related disorderseng
dc.subjectprecisioneng
dc.subjecttailored efficacyeng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleβ-Arrestin Based Receptor Signaling Paradigms: Potential Therapeutic Targets for Complex Age-Related Disordersnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/21727-7
dc.identifier.doi10.3389/fphar.2018.01369none
dc.identifier.doihttp://dx.doi.org/10.18452/20976
dc.type.versionpublishedVersionnone
local.edoc.container-titleFrontiers in Pharmacologynone
local.edoc.pages21none
local.edoc.type-nameZeitschriftenartikel
local.edoc.institutionLebenswissenschaftliche Fakultätnone
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-publisher-nameFrontiers Media S.A.none
local.edoc.container-publisher-placeLausannenone
local.edoc.container-volume9none
dc.description.versionPeer Reviewednone
local.edoc.container-articlenumber1369none
dc.identifier.eissn1663-9812

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