Lopez-Atalaya Jose P, Bhojwani-Cabrera Aysha M
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, Alicante, Spain.
FEBS J. 2025 Apr 29. doi: 10.1111/febs.70126.
Recent evidence suggests that type I interferon (IFN-I) signalling extends beyond its canonical roles in antiviral defence and immunomodulation. Over the past decade, dysregulated IFN-I signalling has been linked to genetic disorders and neurodegenerative diseases, where it may contribute to neurological impairments. Microglia have emerged as key mediators of IFN-I responses in the central nervous system. A distinct transcriptional state responsive to interferons has recently been identified in microglia. The activation of the IFN-I pathway in these cells is now recognised as pivotal in both development and neurodegeneration. This review is divided into two main sections: the first examines the broader role of IFN-I signalling in the central nervous system, particularly its contribution to neurological dysfunction; the second focuses on the specific state of interferon-responsive microglia, exploring its mechanisms and relevance in neurodegenerative conditions. Finally, we discuss how these areas intersect and their implications for both healthy and diseased states.
近期证据表明，I型干扰素（IFN-I）信号传导超出了其在抗病毒防御和免疫调节中的经典作用。在过去十年中，失调的IFN-I信号传导与遗传疾病和神经退行性疾病有关，在这些疾病中它可能导致神经功能障碍。小胶质细胞已成为中枢神经系统中IFN-I反应的关键介质。最近在小胶质细胞中发现了一种对干扰素反应的独特转录状态。现在认为这些细胞中IFN-I途径的激活在发育和神经退行性变中都至关重要。本综述分为两个主要部分：第一部分探讨IFN-I信号传导在中枢神经系统中的更广泛作用，特别是其对神经功能障碍的影响；第二部分关注干扰素反应性小胶质细胞的特定状态，探讨其在神经退行性疾病中的机制和相关性。最后，我们讨论这些领域如何交叉以及它们对健康和疾病状态的影响。
