Kehs Zoe, Cross Abigail C, Li Yue-Ming
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Programs of Pharmacology, Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA.
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Programs of Neuroscience, Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA.
Neurotherapeutics. 2025 Apr;22(3):e00482. doi: 10.1016/j.neurot.2024.e00482. Epub 2024 Nov 8.
Innate immunity protein interferon induced transmembrane protein 3 (IFITM3) is a transmembrane protein that has a wide array of functions, including in viral infections, Alzheimer's Disease (AD), and cancer. As an interferon stimulated gene (ISG), IFITM3's expression is upregulated by type-I, II, and III interferons. Moreover, the antiviral activity of IFITM3 is modulated by post-translational modifications. IFITM3 functions in innate immunity to disrupt viral fusion and entry to the plasma membrane as well as prevent viral escape from endosomes. As a γ-secretase modulatory protein, IFITM3 distinctly modulates the processing of amyloid precursor protein (APP) to generate amyloid beta peptides (Aβ) and Notch1 cleavages. Increased IFITM3 expression, which can result from aging, cytokine activation, inflammation, and infection, can lead to an upregulation of γ-secretase for Aβ production that causes a risk of AD. Therefore, the prevention of IFITM3 upregulation has potential in the development of novel therapies for the treatment of AD.
固有免疫蛋白干扰素诱导跨膜蛋白3（IFITM3）是一种跨膜蛋白，具有广泛的功能，包括在病毒感染、阿尔茨海默病（AD）和癌症方面。作为一种干扰素刺激基因（ISG），IFITM3的表达受到I型、II型和III型干扰素的上调。此外，IFITM3的抗病毒活性受到翻译后修饰的调节。IFITM3在固有免疫中发挥作用，破坏病毒融合并进入质膜，以及防止病毒从内体逃逸。作为一种γ-分泌酶调节蛋白，IFITM3明显调节淀粉样前体蛋白（APP）的加工，以生成淀粉样β肽（Aβ）和Notch1裂解。IFITM3表达增加，这可能由衰老、细胞因子激活、炎症和感染引起，可导致γ-分泌酶上调以产生Aβ，从而导致AD风险。因此，预防IFITM3上调在开发治疗AD的新疗法方面具有潜力。
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