Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disease and clinically manifests with cognitive decline and behavioral disabilities. Over the past years, mounting studies have demonstrated that the inflammatory response plays a key role in the onset and development of AD, and neuroinflammation has been proposed as the third major pathological driving factor of AD, ranking after the two well-known core pathologies, amyloid β (Aβ) deposits and neurofibrillary tangles (NFTs). Epigenetic mechanisms, referring to heritable changes in gene expression independent of DNA sequence alterations, are crucial regulators of neuroinflammation which have emerged as potential therapeutic targets for AD. Upon regulation of transcriptional repression or activation, epigenetic modification profiles are closely involved in inflammatory gene expression and signaling pathways of neuronal differentiation and cognitive function in central nervous system disorders. In this review, we summarize the current knowledge about epigenetic control mechanisms with a focus on DNA and histone modifications involved in the regulation of inflammatory genes and signaling pathways in AD, and the inhibitors under clinical assessment are also discussed.

Alzheimer’s disease (AD) is a progressive degenerative disease of the nervous system that affects older adults. Its main clinical manifestations include memory loss, cognitive dysfunction, abnormal behaviour, and social dysfunction. Neuroinflammation is typical in most neurodegenerative diseases, such as AD. Therefore, suppressing inflammation may improve AD symptoms. This study investigated the neuroprotective effects of Acanthopanax senticosus saponins (ASS) in an AD model induced by streptozotocin (STZ). Here, we characterised a rat model of STZ-induced AD with the parallel deterioration of memory loss and neuroinflammation. Following the end of the treatment with ASS (50 mg/kg for 14 consecutive days), behavioural tests (Morris water maze test, Y-maze test) were performed on the rat, and the molecular parameters (DAPK1, Tau5, p-Tau, NF-κB, IL-1β, TNF-α, and NLRP3) of the rat hippocampus were also assessed. We demonstrated that ASS, which has potent anti-inflammatory effects, can reduce neuroinflammation and prevent cognitive impairment. In the water maze test, ASS-treated groups exhibited significantly increased average escape latency (p < 0.05), the percentage of stay in the target quadrant (p < 0.05), and the number of times each group of rats crossed the platform (p < 0.05) compared to the negative control. And ASS could reduce the phosphorylation of the Tau protein (p < 0.001) and death-associated protein kinase 1 (DAPK1, p < 0.001) in the hippocampal tissue, improving cognitive impairment in STZ-treated rats by suppressing the inflammatory response; the molecular analysis showed a significant reduction in pro-inflammatory markers like NLRP3, IL-1β, TNF-α, and NF-κB (p < 0.001). It was also discovered that the NF-κB inhibitor SN50 had the same effect. Therefore, the present study used ASS through its anti-inflammatory effects to prevent and treat AD. This study highlights the potential efficacy of ASS in alleviating cognitive dysfunction in AD.