Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, New South Wales, Australia.
Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Immunol Rev. 2024 Oct;327(1):83-99. doi: 10.1111/imr.13413. Epub 2024 Oct 29.
Aicardi-Goutières syndrome (AGS) is a progressive genetic encephalopathy caused by pathogenic mutations in genes controlling cellular anti-viral responses and nucleic acid metabolism. The mutations initiate autoinflammatory processes in the brain and systemically that are triggered by chronic overproduction of type I interferon (IFN), including IFN-alpha. Emerging disease-directed therapies aim to dampen autoinflammation and block cellular responses to IFN production, creating an urgent and unmet need to understand better which cells, compartments, and mechanisms underlying disease pathogenesis. In this review, we highlight existing pre-clinical models of AGS and our current understanding of how causative genetic mutations promote disease in AGS, to promote new model development and a continued focus on improving and directing future therapies.
Aicardi-Goutières 综合征（AGS）是一种进行性遗传性脑病，由控制细胞抗病毒反应和核酸代谢的基因中的致病性突变引起。这些突变会在大脑和全身引发自身炎症过程，其触发因素是 I 型干扰素（IFN）的慢性过度产生，包括 IFN-α。新兴的疾病导向疗法旨在抑制自身炎症并阻断细胞对 IFN 产生的反应，因此迫切需要更好地了解疾病发病机制的基础细胞、隔室和机制。在这篇综述中，我们强调了现有的 AGS 临床前模型，以及我们目前对致病基因突变如何促进 AGS 疾病的理解，以促进新模型的开发，并持续关注改进和指导未来的治疗方法。
