Sirkis Daniel W, Oddi Alexis P, Jonson Caroline, Bonham Luke W, Hoang Phuong T, Yokoyama Jennifer S
Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States.
Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, United States.
Front Psychiatry. 2024 Oct 3;15:1480438. doi: 10.3389/fpsyt.2024.1480438. eCollection 2024.
Recent advances in transcriptomics research have uncovered heightened interferon (IFN) responses in neurodegenerative diseases including Alzheimer's disease, primary tauopathy, Parkinson's disease, TDP-43 proteinopathy, and related mouse models. Augmented IFN signaling is now relatively well established for microglia in these contexts, but emerging work has highlighted a novel role for IFN-responsive T cells in the brain and peripheral blood in some types of neurodegeneration. These findings complement a body of literature implicating dysregulated IFN signaling in neuropsychiatric disorders including major depression and post-traumatic stress disorder. In this review, we will characterize and integrate advances in our understanding of IFN responses in neurodegenerative and neuropsychiatric disease, discuss how sex and ancestry modulate the IFN response, and examine potential mechanistic explanations for the upregulation of antiviral-like IFN signaling pathways in these seemingly non-viral neurological and psychiatric disorders.
转录组学研究的最新进展揭示，在包括阿尔茨海默病、原发性tau蛋白病、帕金森病、TDP-43蛋白病以及相关小鼠模型在内的神经退行性疾病中，干扰素（IFN）反应增强。在这些情况下，小胶质细胞中增强的IFN信号传导现已相对明确，但新出现的研究突出了IFN反应性T细胞在某些类型神经退行性疾病的大脑和外周血中的新作用。这些发现补充了一系列将IFN信号失调与包括重度抑郁症和创伤后应激障碍在内的神经精神疾病联系起来的文献。在本综述中，我们将描述并整合我们对神经退行性和神经精神疾病中IFN反应的理解进展，讨论性别和血统如何调节IFN反应，并研究在这些看似非病毒性的神经和精神疾病中抗病毒样IFN信号通路上调的潜在机制解释。
