Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Brain Res. 2024 Feb 1;1824:148686. doi: 10.1016/j.brainres.2023.148686. Epub 2023 Nov 24.
Alzheimer's disease (AD) is a multifactorial,neurodegenerative disorder linked withextracellular amyloid beta (Aβ) plaques deposition and formation of intracellular neurofibrillary tangles (NFTs). Currently, no effective therapies are available to cure AD. Neuroinflammation isa well-known hallmark in the onset and advancement of AD and triggering receptor expressed on myeloid cells-2 (TREM-2), a microglial gene, is responsible for regulating inflammatory responses and clearance of cellular debris. Loss of TREM-2functionincreases neuroinflammation associated expression of pro-inflammatory markersthus resultingin reduced clearance of Aβ that further aid in disease progression.Therefore, targeting neuroinflammation is a good therapeutic approach for AD. This study aimed to determine the neuroprotective effect of nicotinic acid (NA) in vitro model of AD-like pathology induced in F-98 cell line using Phytohemagglutinin (PHA). MTT assay was employed for checking the cell viability as well as the proliferation of the cells following treatment with NA. PHA at the concentration of 10 μg/mL produces maximum plaques. The neuroprotective effect of NA was next evaluated against PHA-induced plaques and it was observed that NA reverses the damages induced by PHA i.e., by inhibiting the clustering of the cells and replacing the damaged cells with the new ones. Further, NA also increased the expression of TREM-2/DAP-12 with parallel decreased in the expression of IL-1β, TNF-α and iNOS. It also successfully altered disease associated ADAM-10 and BACE-1 compared to PHA control. These findings suggest that NA might be considered as a good therapeutic candidate for the treatment of neurodegenerative disorders like AD.
阿尔茨海默病（AD）是一种多因素的神经退行性疾病，与细胞外淀粉样β（Aβ）斑块沉积和细胞内神经原纤维缠结（NFTs）的形成有关。目前，尚无有效的治疗方法可以治愈 AD。神经炎症是 AD 发病和进展的一个众所周知的标志，触发髓样细胞表达的受体-2（TREM-2），一种小胶质细胞基因，负责调节炎症反应和细胞碎片的清除。TREM-2 功能的丧失会增加与神经炎症相关的促炎标志物的表达，从而导致 Aβ的清除减少，进一步促进疾病的进展。因此，针对神经炎症是 AD 的一种很好的治疗方法。本研究旨在确定烟酸（NA）在 F-98 细胞系中诱导的 AD 样病理体外模型中的神经保护作用，使用植物血球凝集素（PHA）。MTT 测定法用于检查细胞活力以及细胞增殖情况，观察到 NA 逆转了 PHA 诱导的斑块的损伤，即抑制细胞聚集并用新细胞取代受损细胞。此外，NA 还增加了 TREM-2/DAP-12 的表达，同时降低了 IL-1β、TNF-α 和 iNOS 的表达。与 PHA 对照组相比，它还成功改变了与疾病相关的 ADAM-10 和 BACE-1。这些发现表明，NA 可能被认为是治疗 AD 等神经退行性疾病的一种良好的治疗候选药物。
