College of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Department of Neurology, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China.
Neurochem Res. 2024 Oct;49(10):2888-2896. doi: 10.1007/s11064-024-04210-z. Epub 2024 Jul 22.
With the aging global population, Alzheimer's disease (AD) has become a significant social and economic burden, necessitating the development of novel therapeutic strategies. This study investigates the therapeutic potential of nicotinamide mononucleotide (NMN) synbiotics, a combination of NMN, Lactiplantibacillus plantarum CGMCC 1.16089, and lactulose, in mitigating AD pathology. APP/PS1 mice were supplemented with NMN synbiotics and compared against control groups. The effects on amyloid-β (Aβ) deposition, intestinal histopathology, tight junction proteins, inflammatory cytokines, and reactive oxygen species (ROS) levels were assessed. NMN synbiotics intervention significantly reduced Aβ deposition in the cerebral cortex and hippocampus by 67% and 60%, respectively. It also ameliorated histopathological changes in the colon, reducing crypt depth and restoring goblet cell numbers. The expression of tight junction proteins Claudin-1 and ZO-1 was significantly upregulated, enhancing intestinal barrier integrity. Furthermore, NMN synbiotics decreased the expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α, and reduced ROS levels, indicative of attenuated oxidative stress. The reduction in Aβ deposition, enhancement of intestinal barrier function, decrease in neuroinflammation, and alleviation of oxidative stress suggest that NMN synbiotics present a promising therapeutic intervention for AD by modulating multiple pathological pathways. Further research is required to elucidate the precise mechanisms, particularly the role of the NLRP3 inflammasome pathway, which may offer a novel target for AD treatment.
随着全球人口老龄化，阿尔茨海默病（AD）已成为重大的社会和经济负担，因此需要开发新的治疗策略。本研究探讨了烟酰胺单核苷酸（NMN）共生体（NMN 与植物乳杆菌 CGMCC 1.16089 和乳果糖的组合）在缓解 AD 病理方面的治疗潜力。将 APP/PS1 小鼠补充 NMN 共生体，并与对照组进行比较。评估了对淀粉样蛋白-β（Aβ）沉积、肠道组织病理学、紧密连接蛋白、炎症细胞因子和活性氧（ROS）水平的影响。NMN 共生体干预可使大脑皮层和海马体中的 Aβ沉积分别减少 67%和 60%。它还改善了结肠的组织病理学变化，降低了隐窝深度并恢复了杯状细胞数量。紧密连接蛋白 Claudin-1 和 ZO-1 的表达显著上调，增强了肠道屏障完整性。此外，NMN 共生体降低了促炎细胞因子 IL-1β、IL-6 和 TNF-α 的表达，并降低了 ROS 水平，表明氧化应激减轻。Aβ 沉积减少、肠道屏障功能增强、神经炎症减轻和氧化应激缓解表明，NMN 共生体通过调节多种病理途径为 AD 提供了一种有前途的治疗干预措施。需要进一步研究来阐明确切的机制，特别是 NLRP3 炎性小体途径的作用，这可能为 AD 治疗提供新的靶点。
