Next Article in Journal
Oxidative Insults and Mitochondrial DNA Mutation Promote Enhanced Autophagy and Mitophagy Compromising Cell Viability in Pluripotent Cell Model of Mitochondrial Disease
Previous Article in Journal
Bone Marrow Derived Extracellular Vesicles Activate Osteoclast Differentiation in Traumatic Brain Injury Induced Bone Loss
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle
Cells 2019, 8(1), 64; https://doi.org/10.3390/cells8010064

Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1

1
Oasi Research Institute—IRCCS, 94018 Troina, Italy
2
Ralph N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047-1620, USA
3
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047-1620, USA
4
Bio-nanotech Research and Innovation Tower (BRIT), University of Catania, 95125 Catania, Italy
5
Department of Drug Sciences, University of Catania, 95125 Catania, Italy
6
Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95125 Catania, Italy
7
Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, 95125 Catania, Italy
8
Department of Chemistry, University of Kansas, Lawrence, KS 66047-1620, USA
*
Authors to whom correspondence should be addressed.
Current address: Department of Biomedical and Biotechnological Sciences, PhD Program in Neurosciences, University of Catania, 95125 Catania, Italy.
Received: 28 December 2018 / Revised: 12 January 2019 / Accepted: 14 January 2019 / Published: 17 January 2019
(This article belongs to the Special Issue TGF-beta/BMP Signaling Pathway)
Full-Text   |   PDF [2225 KB, uploaded 17 January 2019]   |  

Abstract

Carnosine (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. View Full-Text
Keywords: carnosine; microglia; Alzheimer’s disease; neurodegeneration; neuroinflammation; reactive oxygen and nitrogen species; oxidative stress; TGF-β1 carnosine; microglia; Alzheimer’s disease; neurodegeneration; neuroinflammation; reactive oxygen and nitrogen species; oxidative stress; TGF-β1
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Caruso, 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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top