biostudies-literatureCheng LNatural Science Foundation of Shandong Provincethe Fundamental Research Funds of Chinese Academy of Medical SciencesShandong University Multidisciplinary Research and Innovation Team of Young Scholarsthe National Natural Science Foundation of China135https://www.ebi.ac.uk/biostudies/studies/S-EPMC11971201biostudies-literatureUnknown50(2)The accumulation of amyloid β (Aβ) protein, derived from the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) by inducing neuronal cell injury. This study investigated the specific functions of ubiquitin-specific protease 1-associated factor 1 (UAF1) in mediating the neurotoxic effects triggered on Aβ. To model AD-related neuronal injury in vitro and in vitro, SH-SY5Y cells exposed to Aβ_25-35 and APPswe/PS1dE9 (APP/PS1) transgenic mice were utilized. Compared with control mice, UAF1 levels were significantly elevated in the hippocampus of experimental mice. In vitro experiments showed that UAF1 knockdown reduced Aβ-induced apoptosis and enhanced cell viability. Furthermore, UAF1 knockdown markedly suppressed Aβ_25-35Neurochemical researchTargeting UAF1 Alleviate Neurotoxicity by Inhibiting APP/NLRP3 Axis-Mediated Pyroptosis and Apoptosis.PMC11971201818708482020QNQT0192019-RC-HL-026ZR2023MH340Yang HXiao YLi FXie ZCheng LZheng BTian DMeng XBi JZhao XXu YfalseTargeting UAF1 Alleviate Neurotoxicity by Inhibiting APP/NLRP3 Axis-Mediated Pyroptosis and Apoptosis.The accumulation of amyloid β (Aβ) protein, derived from the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) by inducing neuronal cell injury. This study investigated the specific functions of ubiquitin-specific protease 1-associated factor 1 (UAF1) in mediating the neurotoxic effects triggered on Aβ. To model AD-related neuronal injury in vitro and in vitro, SH-SY5Y cells exposed to Aβ_25-35 and APPswe/PS1dE9 (APP/PS1) transgenic mice were utilized. Compared with control mice, UAF1 levels were significantly elevated in the hippocampus of experimental mice. In vitro experiments showed that UAF1 knockdown reduced Aβ-induced apoptosis and enhanced cell viability. Furthermore, UAF1 knockdown markedly suppressed Aβ_25-352025-01-01T00:00:00Z2025 Apr2025-07-03T03:04:32.272Z2025-07-03T03:04:32.272ZS-EPMC119712014018384110.1007/s11064-025-04379-x