Show simple item record

dc.contributor.authorCaruso, Giuseppe
dc.contributor.authorFresta, Claudia G.
dc.contributor.authorMusso, Nicolò
dc.contributor.authorGiambirtone, Mariaconcetta
dc.contributor.authorGrasso, Margherita
dc.contributor.authorSpampinato, Simona F.
dc.contributor.authorMerlo, Sara
dc.contributor.authorDrago, Filippo
dc.contributor.authorLazzarino, Giuseppe
dc.contributor.authorSortino, Maria A.
dc.contributor.authorLunte, Susan M.
dc.contributor.authorCaraci, Filippo
dc.date.accessioned2021-01-06T19:14:11Z
dc.date.available2021-01-06T19:14:11Z
dc.date.issued2019-01-17
dc.identifier.citationCaruso, G.; Fresta, C.G.; Musso, N.; Giambirtone, M.; Grasso, M.; Spampinato, S.F.; Merlo, S.; Drago, F.; Lazzarino, G.; Sortino, M.A.; Lunte, S.M.; Caraci, F. Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1. Cells 2019, 8, 64.en_US
dc.identifier.urihttp://hdl.handle.net/1808/31043
dc.descriptionThis work is licensed under a Creative Commons Attribution 4.0 International License.en_US
dc.description.abstractCarnosine (β-alanyl-L-histidine), a dipeptide, is an endogenous antioxidant widely distributed in excitable tissues like muscles and the brain. Carnosine is involved in cellular defense mechanisms against oxidative stress, including the inhibition of amyloid-beta (Aβ) aggregation and the scavenging of reactive species. Microglia play a central role in the pathogenesis of Alzheimer’s disease, promoting neuroinflammation through the secretion of inflammatory mediators and free radicals. However, the effects of carnosine on microglial cells and neuroinflammation are not well understood. In the present work, carnosine was tested for its ability to protect BV-2 microglial cells against oligomeric Aβ1-42-induced oxidative stress and inflammation. Carnosine prevented cell death in BV-2 cells challenged with Aβ oligomers through multiple mechanisms. Specifically, carnosine lowered the oxidative stress by decreasing NO and O2−• intracellular levels as well as the expression of iNOS and Nox enzymes. Carnosine also decreased the secretion of pro-inflammatory cytokines such as IL-1β, simultaneously rescuing IL-10 levels and increasing the expression and the release of TGF-β1. Carnosine also prevented Aβ-induced neurodegeneration in mixed neuronal cultures challenged with Aβ oligomers, and these neuroprotective effects were completely abolished by SB431542, a selective inhibitor of the type-1 TGF-β receptor. Our data suggest a multimodal mechanism of action of carnosine underlying its protective effects on microglial cells against Aβ toxicity with a key role of TGF-β1 in mediating these protective effects.en_US
dc.publisherMDPIen_US
dc.rights© 2019 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectCarnosineen_US
dc.subjectMicrogliaen_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectNeurodegenerationen_US
dc.subjectNeuroinflammationen_US
dc.subjectReactive oxygen and nitrogen speciesen_US
dc.subjectOxidative stressen_US
dc.subjectTGF-β1en_US
dc.titleCarnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1en_US
dc.typeArticleen_US
kusw.kuauthorLunte, Susan M.
kusw.kudepartmentChemistryen_US
kusw.kudepartmentHiguchi Biosciences Centeren_US
kusw.kudepartmentPharmaceutical Chemistryen_US
dc.identifier.doi10.3390/cells8010064en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-1571-5327en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-6558-9800en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-5917-7279en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-2734-1521en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.rights.accessrightsopenAccessen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Except where otherwise noted, this item's license is described as: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.