Zhang Yadan, Zhang Xiaoyu, Zhou Jie, Li Yuting, Kai Tianhan, Zhang Lin
College of Food Science and Engineering, Hunan Key Laboratory of Processed Food for Special Medical Purpose, Central South University of Forestry and Technology, Changsha 410004, China.
Xiang Ya School of Public Health, Central South University, Changsha 410078, China.
Int J Biol Macromol. 2025 Apr;304(Pt 1):140758. doi: 10.1016/j.ijbiomac.2025.140758. Epub 2025 Feb 6.
Alzheimer's disease (AD) is predominantly characterized by cholinergic dysfunction, mitochondrial impairment, oxidative stress, and inflammation, primarily driven by amyloid-beta (Aβ) peptides. This study investigates the protective effects of Lycium ruthenicum Murray-derived exosome-like nanoparticles (LELN) in AD models using transgenic Caenorhabditis elegans (C. elegans). Findings showed that C. elegans effectively internalized LELN, which remained stable in vivo. Compared with untreated controls, treatment with 600 μg/mL LELN significantly extended the lifespan of CL4176 [myo-3p::Aβ] and CL2006 [unc-54/Aβ] worms by 34.78 % and 34.85 %, respectively, and delayed Aβ-induced paralysis by 52.42 % and 42.72 %, respectively. Furthermore, LELN increased the chemotaxis index of CL2355 [snb-1::Aβ] worms from 11.11 % to 55.56 %. Mechanistically, LELN reduced the levels of Aβ oligomers and monomers via the DAF-16 pathway, consequently alleviating AD-like symptoms in transgenic C. elegans. The effects of LELN include inhibiting acetylcholinesterase activity to mitigate cholinergic dysfunction, restoring mitochondrial membrane potential and adenosine triphosphate production to ameliorate mitochondrial dysfunction, and reducing oxidative stress and inflammation. Collectively, these results highlight the protective role of LELN against Aβ-induced AD pathology and underscore their potential as a therapeutic candidate for AD treatment.
阿尔茨海默病（AD）的主要特征是胆碱能功能障碍、线粒体损伤、氧化应激和炎症，主要由β-淀粉样蛋白（Aβ）肽驱动。本研究使用转基因秀丽隐杆线虫（C. elegans）研究了黑果枸杞来源的外泌体样纳米颗粒（LELN）在AD模型中的保护作用。研究结果表明，秀丽隐杆线虫能有效内化LELN，且LELN在体内保持稳定。与未处理的对照组相比，用600μg/mL LELN处理可使CL4176 [myo-3p::Aβ]和CL2006 [unc-54/Aβ]线虫的寿命分别显著延长34.78%和34.85%，并使Aβ诱导的麻痹分别延迟52.42%和42.72%。此外，LELN使CL2355 [snb-1::Aβ]线虫的趋化指数从11.11%提高到55.56%。从机制上讲，LELN通过DAF-16途径降低了Aβ寡聚体和单体的水平，从而减轻了转基因秀丽隐杆线虫的AD样症状。LELN的作用包括抑制乙酰胆碱酯酶活性以减轻胆碱能功能障碍，恢复线粒体膜电位和三磷酸腺苷生成以改善线粒体功能障碍，以及减少氧化应激和炎症。总的来说，这些结果突出了LELN对Aβ诱导的AD病理的保护作用，并强调了它们作为AD治疗候选药物的潜力。
