دورية أكاديمية
The potential therapeutic role of itaconate and mesaconate on the detrimental effects of LPS-induced neuroinflammation in the brain.
العنوان: | The potential therapeutic role of itaconate and mesaconate on the detrimental effects of LPS-induced neuroinflammation in the brain. |
---|---|
المؤلفون: | Ohm M; Department of Cellular Neurobiology, Zoological Institute, TU Braunschweig, 38106, Braunschweig, Germany., Hosseini S; Department of Cellular Neurobiology, Zoological Institute, TU Braunschweig, 38106, Braunschweig, Germany.; Neuroinflammation and Neurodegeneration Group, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany., Lonnemann N; Department of Cellular Neurobiology, Zoological Institute, TU Braunschweig, 38106, Braunschweig, Germany., He W; Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), TU Braunschweig, 38106, Braunschweig, Germany., More T; Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), TU Braunschweig, 38106, Braunschweig, Germany., Goldmann O; Infection Immunology Research Group, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany., Medina E; Infection Immunology Research Group, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany., Hiller K; Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), TU Braunschweig, 38106, Braunschweig, Germany. karsten.hiller@tu-braunschweig.de., Korte M; Department of Cellular Neurobiology, Zoological Institute, TU Braunschweig, 38106, Braunschweig, Germany. m.korte@tu-braunschweig.de.; Neuroinflammation and Neurodegeneration Group, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany. m.korte@tu-braunschweig.de. |
المصدر: | Journal of neuroinflammation [J Neuroinflammation] 2024 Aug 20; Vol. 21 (1), pp. 207. Date of Electronic Publication: 2024 Aug 20. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101222974 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-2094 (Electronic) Linking ISSN: 17422094 NLM ISO Abbreviation: J Neuroinflammation Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : BioMed Central, c2004- |
مواضيع طبية MeSH: | Succinates*/pharmacology , Succinates*/therapeutic use , Neuroinflammatory Diseases*/drug therapy , Neuroinflammatory Diseases*/metabolism , Neuroinflammatory Diseases*/pathology , Neuroinflammatory Diseases*/chemically induced , Neuroinflammatory Diseases*/immunology , Lipopolysaccharides*/toxicity, Animals ; Brain/drug effects ; Brain/metabolism ; Brain/pathology ; Brain/immunology ; Mice ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Male ; Mice, Inbred C57BL |
مستخلص: | Despite advances in antimicrobial and anti-inflammatory treatment, inflammation and its consequences remain a major challenge in the field of medicine. Inflammatory reactions can lead to life-threatening conditions such as septic shock, while chronic inflammation has the potential to worsen the condition of body tissues and ultimately lead to significant impairment of their functionality. Although the central nervous system has long been considered immune privileged to peripheral immune responses, recent research has shown that strong immune responses in the periphery also affect the brain, leading to reactive microglia, which belong to the innate immune system and reside in the brain, and neuroinflammation. The inflammatory response is primarily a protective mechanism to defend against pathogens and tissue damage. However, excessive and chronic inflammation can have negative effects on neuronal structure and function. Neuroinflammation underlies the pathogenesis of many neurological and neurodegenerative diseases and can accelerate their progression. Consequently, targeting inflammatory signaling pathways offers potential therapeutic strategies for various neuropathological conditions, particularly Parkinson's and Alzheimer's disease, by curbing inflammation. Here the blood-brain barrier is a major hurdle for potential therapeutic strategies, therefore it would be highly advantageous to foster and utilize brain innate anti-inflammatory mechanisms. The tricarboxylic acid cycle-derived metabolite itaconate is highly upregulated in activated macrophages and has been shown to act as an immunomodulator with anti-inflammatory and antimicrobial functions. Mesaconate, an isomer of itaconate, similarly reduces the inflammatory response in macrophages. Nevertheless, most studies have focused on its esterified forms and its peripheral effects, while its influence on the CNS remained largely unexplored. Therefore, this study investigated the immunomodulatory and therapeutic potential of endogenously synthesized itaconate and its isomer mesaconate in lipopolysaccharide (LPS)-induced neuroinflammatory processes. Our results show that both itaconate and mesaconate reduce LPS-induced neuroinflammation, as evidenced by lower levels of inflammatory mediators, reduced microglial reactivity and a rescue of synaptic plasticity, the cellular correlate of learning and memory processes in the brain. Overall, this study emphasizes that both itaconate and mesaconate have therapeutic potential for neuroinflammatory processes in the brain and are of remarkable importance due to their endogenous origin and production, which usually leads to high tolerance. (© 2024. The Author(s).) |
References: | Elife. 2022 Aug 30;11:. (PMID: 36040311) Molecules. 2022 Aug 26;27(17):. (PMID: 36080253) PLoS Pathog. 2022 Jan 13;18(1):e1010219. (PMID: 35025971) Neuropathol Appl Neurobiol. 2013 Feb;39(1):51-68. (PMID: 23046210) Cell Metab. 2016 Jul 12;24(1):158-66. (PMID: 27374498) J Neural Transm (Vienna). 2018 May;125(5):781-795. (PMID: 28534174) Inflammopharmacology. 2024 Feb;32(1):419-432. (PMID: 37470905) Immunity. 2019 Jan 15;50(1):64-76.e4. (PMID: 30635240) Brain Commun. 2021 Aug 19;3(3):fcab187. (PMID: 34557667) Cytokine Growth Factor Rev. 2002 Aug-Oct;13(4-5):413-21. (PMID: 12220554) Brain Res. 2007 Jan 26;1130(1):158-66. (PMID: 17174281) Inflammation. 2023 Aug;46(4):1177-1191. (PMID: 37142886) J Neuroimmunol. 2006 Jun;175(1-2):97-106. (PMID: 16626814) J Biol Chem. 2000 Aug 25;275(34):26252-8. (PMID: 10856294) Nature. 2017 Jan 26;541(7638):481-487. (PMID: 28099414) Glia. 2016 Feb;64(2):300-16. (PMID: 26470014) Int J Mol Sci. 2019 Nov 28;20(23):. (PMID: 31795299) J Clin Invest. 2022 Jan 18;132(2):. (PMID: 35040439) Sci Adv. 2023 Apr 28;9(17):eadg0654. (PMID: 37115931) J Neurochem. 2005 Apr;93(1):221-31. (PMID: 15773921) Anal Chem. 2009 May 1;81(9):3429-39. (PMID: 19358599) Cell Metab. 2022 Mar 1;34(3):487-501.e8. (PMID: 35235776) Int J Mol Sci. 2023 Nov 06;24(21):. (PMID: 37958978) Front Cell Neurosci. 2019 Aug 07;13:363. (PMID: 31440144) Crit Rev Immunol. 2012;32(1):23-63. (PMID: 22428854) Nature. 2018 Apr 5;556(7699):113-117. (PMID: 29590092) Nature. 2018 Apr;556(7701):332-338. (PMID: 29643512) Molecules. 2022 May 17;27(10):. (PMID: 35630670) Glia. 2013 Jun;61(6):855-68. (PMID: 23536230) Neuroscience. 2001;102(2):273-80. (PMID: 11166113) Int Immunopharmacol. 2021 Nov;100:108116. (PMID: 34500285) Hippocampus. 2003;13(7):826-34. (PMID: 14620878) Physiol Rev. 2014 Oct;94(4):1077-98. (PMID: 25287860) Proc Natl Acad Sci U S A. 2020 Dec 15;117(50):32145-32154. (PMID: 33257576) Trends Pharmacol Sci. 2008 Aug;29(8):402-12. (PMID: 18617277) Mol Psychiatry. 2000 Nov;5(6):604-15. (PMID: 11126391) Lancet Neurol. 2015 Apr;14(4):388-405. (PMID: 25792098) Nat Metab. 2022 May;4(5):534-546. (PMID: 35655026) Metabolites. 2022 Nov 02;12(11):. (PMID: 36355140) J Neurol Neurosurg Spine. 2016;1(1):. (PMID: 28127589) Acta Neuropathol Commun. 2023 Apr 28;11(1):69. (PMID: 37118836) Front Cell Neurosci. 2020 Aug 06;14:198. (PMID: 32848611) J Neurosci. 2012 Mar 21;32(12):3958-68. (PMID: 22442063) J Biol Chem. 2003 May 23;278(21):19453-62. (PMID: 12609991) Front Cell Neurosci. 2017 Jul 24;11:216. (PMID: 28790893) Curr Neuropharmacol. 2016;14(2):155-64. (PMID: 26639457) Curr Protoc Mouse Biol. 2016 Sep 01;6(3):333-342. (PMID: 27584556) Nat Rev Immunol. 2007 Feb;7(2):161-7. (PMID: 17220915) Mol Metab. 2020 Feb;32:122-135. (PMID: 32029222) Microb Pathog. 2019 Aug;133:103541. (PMID: 31100405) Physiol Rev. 2011 Apr;91(2):461-553. (PMID: 21527731) Neuron. 2022 Nov 2;110(21):3458-3483. (PMID: 36327895) Trends Immunol. 2016 Sep;37(9):608-620. (PMID: 27443914) Brain Sci. 2022 Sep 16;12(9):. (PMID: 36138991) Physiol Rev. 2018 Jan 1;98(1):477-504. (PMID: 29351513) FASEB J. 2016 Jan;30(1):286-300. (PMID: 26358042) Sci Rep. 2019 Apr 8;9(1):5790. (PMID: 30962497) Lab Anim Res. 2019 Oct 16;35:19. (PMID: 32257907) Vitam Horm. 2002;64:185-219. (PMID: 11898392) J Biol Chem. 2016 Feb 19;291(8):3932-46. (PMID: 26679997) Hepatology. 2020 Oct;72(4):1394-1411. (PMID: 31997373) Immunol Rev. 2006 Oct;213:48-65. (PMID: 16972896) Nature. 2018 Apr;556(7702):501-504. (PMID: 29670287) Neuroimmunomodulation. 2009 Jan;16(1):1-12. (PMID: 19077440) Int J Mol Sci. 2019 May 09;20(9):. (PMID: 31075861) Int J Mol Sci. 2022 Apr 15;23(8):. (PMID: 35457208) Redox Biol. 2023 Oct;66:102863. (PMID: 37672892) J Neurosci. 2018 Mar 21;38(12):3060-3080. (PMID: 29487124) Nat Metab. 2022 May;4(5):524-533. (PMID: 35655024) Lab Invest. 2017 Jan;97(1):4-13. (PMID: 27869795) Mol Med Rep. 2016 Apr;13(4):3391-6. (PMID: 26935478) Proc Natl Acad Sci U S A. 2013 May 7;110(19):7820-5. (PMID: 23610393) Am J Transl Res. 2021 Mar 15;13(3):1155-1169. (PMID: 33841646) Neuroscientist. 2014 Apr;20(2):160-72. (PMID: 24106265) Front Pharmacol. 2023 Mar 29;14:1142639. (PMID: 37063291) Neuroreport. 1997 Jul 7;8(9-10):2107-10. (PMID: 9243593) Cold Spring Harb Perspect Biol. 2014 Nov 07;7(2):a020420. (PMID: 25380660) Brain Behav Immun Health. 2020 Mar 18;4:100060. (PMID: 34589845) Int Anesthesiol Clin. 2007 Spring;45(2):27-37. (PMID: 17426506) J Neurosci. 2020 Jul 8;40(28):5480-5494. (PMID: 32499379) MethodsX. 2014 Jul 18;1:74-80. (PMID: 26150938) Nat Metab. 2020 Jul;2(7):594-602. (PMID: 32694786) Biochem Biophys Res Commun. 2016 Oct 14;479(2):331-337. (PMID: 27641666) Sci Immunol. 2020 Oct 23;5(52):. (PMID: 33097591) Mol Psychiatry. 2009 May;14(5):511-22. (PMID: 18195714) Clin Exp Immunol. 2022 Oct 21;210(1):24-38. (PMID: 35802780) Front Integr Neurosci. 2013 Aug 23;7:61. (PMID: 23986663) Mediators Inflamm. 2013;2013:271359. (PMID: 23935246) Science. 2005 May 27;308(5726):1314-8. (PMID: 15831717) Front Cell Neurosci. 2021 Apr 28;15:643650. (PMID: 33994946) |
معلومات مُعتمدة: | SPP2395 German Research Foundation (Deutsche Forschungsgemeinschaft); SPP2395 German Research Foundation (Deutsche Forschungsgemeinschaft) |
فهرسة مساهمة: | Keywords: Hippocampus; LPS; Microglia; Neuroinflammation; Synaptic plasticity |
المشرفين على المادة: | Q4516562YH (itaconic acid) 0 (Succinates) 0 (Lipopolysaccharides) 0 (Anti-Inflammatory Agents) |
تواريخ الأحداث: | Date Created: 20240820 Date Completed: 20240821 Latest Revision: 20240823 |
رمز التحديث: | 20240823 |
مُعرف محوري في PubMed: | PMC11337794 |
DOI: | 10.1186/s12974-024-03188-3 |
PMID: | 39164713 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1742-2094 |
---|---|
DOI: | 10.1186/s12974-024-03188-3 |