دورية أكاديمية
أعرض في EDS

The potential therapeutic role of itaconate and mesaconate on the detrimental effects of LPS-induced neuroinflammation in the brain.

التفاصيل البيبلوغرافية
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).)
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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
الوصف
تدمد:1742-2094
DOI:10.1186/s12974-024-03188-3