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Type I interferon (IFN)-inducible Absent in Melanoma 2 proteins in neuroinflammation: implications for Alzheimer’s disease
Cumulative evidence indicates that activation of innate immune responses in the central nervous system (CNS) induces the expression of type 1 interferons (T1 IFNs), a family of cytokines. The T1 IFNs (IFN-α/β), through activation of the JAK/STAT-signaling in microglia, astrocytes, and neurons, induc...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880379/ https://www.ncbi.nlm.nih.gov/pubmed/31771614 http://dx.doi.org/10.1186/s12974-019-1639-5 |
Sumario: | Cumulative evidence indicates that activation of innate immune responses in the central nervous system (CNS) induces the expression of type 1 interferons (T1 IFNs), a family of cytokines. The T1 IFNs (IFN-α/β), through activation of the JAK/STAT-signaling in microglia, astrocytes, and neurons, induce the expression of IFN-inducible proteins, which mediate the pro- and anti-inflammatory functions of IFNs. Accordingly, T1 IFN-inducible Absent in Melanoma 2 proteins (murine Aim2 and human AIM2) negatively regulate the expression of TI IFNs and, upon sensing higher levels of cytosolic DNA, assemble the Aim2/AIM2 inflammasome, resulting in activation of caspase-1, pyroptosis, and the secretion of pro-inflammatory cytokines (e.g., IL-1β and IL-18). Of interest, studies have indicated a role for the Aim2/AIM2 proteins in neuroinflammation and neurodegenerative diseases, including Alzheimer’s disease (AD). The ability of Aim2/AIM2 proteins to exert pro- and anti-inflammatory effects in CNS may depend upon age, sex hormones, cell-types, and the expression of species-specific negative regulators of the Aim2/AIM2 inflammasome. Therefore, we discuss the role of Aim2/AIM2 proteins in the development of AD. An improved understanding of the role of Absent in Melanoma 2 proteins in AD could identify new approaches to treat patients. |
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