Chitotriosidase (CHIT1, chitinase 1) is increased in the cerebrospinal fluid and peripheral blood of Alzheimer’s disease (AD) patients. Our previous study has shown that CHIT1 provides potential protection through microglial polarization and reduction of β-amyloid (Aβ) oligomers on rat models of AD. Histone deacetylase 3 (HDAC3) plays a significant role in the expression and regulation of proteins related to the pathophysiology of AD. In addition, nuclear factor-kappa B (NF-κB) signaling pathway activation in neurons is associated with the progression of AD. NF-κB activation is regulated by HDAC3 deacetylation. In the present study, we researched the role of CHIT1 in HDAC3/NF-κB signaling in D-galactose (D-gal) and aluminum-exposed rat model with cognitive impairments. Following CHIT1 treatment, we found that the protein and mRNA levels of HDAC3 and NF-κB were reduced, the expression level of IκBα increased, anti-inflammatory factors (Arg-1, IL-10, and CD206) were elevated while pro-inflammatory factors (TNF-a, iNOS, and IL-1β) were decreased in D-gal/aluminum-induced AD rats. These results indicate that CHIT1 can regulate brain inflammation via HDAC3/NF-κB p65 pathway, contributing to improvement of cognitive impairment.

壳三糖苷酶（CHIT1，几丁质酶 1）在阿尔茨海默病 (AD) 患者的脑脊液和外周血中升高。我们之前的研究表明，CHIT1 通过小胶质细胞极化和减少 β-淀粉样蛋白 (Aβ) 寡聚体对 AD 大鼠模型提供潜在保护。组蛋白去乙酰化酶 3 (HDAC3) 在与 AD 病理生理学相关的蛋白质的表达和调节中起重要作用。此外，神经元中的核因子-κB (NF-κB) 信号通路激活与 AD 的进展有关。NF-κB 激活受 HDAC3 脱乙酰化调节。在本研究中，我们研究了 CHIT1 在 D-半乳糖 (D-gal) 和铝暴露的认知障碍大鼠模型中 HDAC3/NF-κB 信号传导中的作用。CHIT1处理后，我们发现 HDAC3 和 NF-κB 的蛋白和 mRNA 水平降低，IκBα 的表达水平升高，抗炎因子（Arg-1、IL-10 和 CD206）升高，而促炎因子（TNF- a、iNOS 和 IL-1β) 在 D-gal/铝诱导的 AD 大鼠中降低。这些结果表明 CHIT1 可以通过 HDAC3/NF-κB p65 通路调节脑炎症，有助于改善认知障碍。