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Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1
Caruso, Giuseppe Fresta, Claudia G. Musso, Nicolò Giambirtone, Mariaconcetta Grasso, Margherita Spampinato, Simona F. Merlo, Sara Drago, Filippo Lazzarino, Giuseppe Sortino, Maria A.
Caruso, Giuseppe
Fresta, Claudia G.
Musso, Nicolò
Giambirtone, Mariaconcetta
Grasso, Margherita
Spampinato, Simona F.
Merlo, Sara
Drago, Filippo
Lazzarino, Giuseppe
Sortino, Maria A.
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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.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
Date
2019-01-17
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MDPI
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Keywords
Carnosine, Microglia, Alzheimer’s disease, Neurodegeneration, Neuroinflammation, Reactive oxygen and nitrogen species, Oxidative stress, TGF-β1
Citation
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. (2019). Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1. Cells, 8(1), 64. https://doi.org/10.3390/cells8010064