Senarath Rathnayaka Mudiyanselage Uththara Sachinthanie, Oikari Lotta E, Bharadwaj Prashant, Jayasena Vijay, Martins Ralph N, Fernando Wanakulasuriya Mary Ann Dipika Binosha
School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia.
Australian Alzheimer's Research, Ralph and Patricia Sarich Neuroscience Research Institute, Nedlands, WA 6009, Australia.
Nutrients. 2025 Jul 10;17(14):2286. doi: 10.3390/nu17142286.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β plaque accumulation, tau tangles, and extensive neuroinflammation. Neuroinflammation, driven by glial cells like microglia and astrocytes, plays a critical role in AD progression. Initially, these cells provide protective functions, such as debris clearance and neurotrophic support. However, as AD progresses, chronic activation of these cells exacerbates inflammation, contributing to synaptic dysfunction, neuronal loss, and cognitive decline. Microglia release pro-inflammatory cytokines and reactive oxygen species (ROS), while astrocytes undergo reactive astrogliosis, further impairing neuronal health. This maladaptive response from glial cells significantly accelerates disease pathology. Current AD treatments primarily aim at symptomatic relief, with limited success in disease modification. While amyloid-targeting therapies like Aducanumab and Lecanemab show some promise, their efficacy remains limited. In this context, natural compounds have gained attention for their potential to modulate neuroinflammation and promote neuroprotection. Among these, butyrate and lauric acid are particularly notable. Butyrate, produced by a healthy gut microbiome, acts as a histone deacetylase (HDAC) inhibitor, reducing pro-inflammatory cytokines and supporting neuronal health. Lauric acid, on the other hand, enhances mitochondrial function, reduces oxidative stress, and modulates inflammatory pathways, thereby supporting glial and neuronal health. Both compounds have been shown to decrease amyloid-β deposition, reduce neuroinflammation, and promote neuroprotection in AD models. This review explores the mechanisms through which butyrate and lauric acid modulate glial and neuronal activity, highlighting their potential as therapeutic agents for mitigating neuroinflammation and slowing AD progression.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征为淀粉样β蛋白斑块积聚、tau蛋白缠结和广泛的神经炎症。由小胶质细胞和星形胶质细胞等胶质细胞驱动的神经炎症在AD进展中起关键作用。最初，这些细胞发挥保护功能，如清除碎片和提供神经营养支持。然而，随着AD的进展，这些细胞的慢性激活会加剧炎症，导致突触功能障碍、神经元丧失和认知衰退。小胶质细胞释放促炎细胞因子和活性氧（ROS），而星形胶质细胞发生反应性星形胶质细胞增生，进一步损害神经元健康。胶质细胞的这种适应不良反应显著加速了疾病病理过程。目前的AD治疗主要旨在缓解症状，在疾病修饰方面取得的成功有限。虽然像阿杜卡单抗和乐卡奈单抗这样的靶向淀粉样蛋白疗法显示出一些希望，但其疗效仍然有限。在这种背景下，天然化合物因其调节神经炎症和促进神经保护的潜力而受到关注。其中，丁酸盐和月桂酸尤为显著。由健康的肠道微生物群产生的丁酸盐作为组蛋白脱乙酰酶（HDAC）抑制剂，可减少促炎细胞因子并支持神经元健康。另一方面，月桂酸可增强线粒体功能、减少氧化应激并调节炎症途径，从而支持胶质细胞和神经元健康。在AD模型中，这两种化合物均已显示出可减少淀粉样β蛋白沉积、减轻神经炎症并促进神经保护。本综述探讨了丁酸盐和月桂酸调节胶质细胞和神经元活动的机制，强调了它们作为减轻神经炎症和减缓AD进展的治疗剂的潜力。
