Tyrosine kinase receptor A (TrkA) plays an important role in the protection of cholinergic neurons in Alzheimer's disease (AD). This study was designed to investigate whether β-hydroxybutyrate (BHB), an endogenous histone deacetylase (HDAC) inhibitor, upregulates the expression of TrkA by affecting histone acetylation in SH-SY5Y cells treated with amyloid β-protein (Aβ). The results showed that BHB ameliorated the reduction of cell vitality and downregulation of TrkA expression induced by Aβ. Furthermore, BHB inhibited the upregulation of HDAC1/2/3 expression and downregulation of histone acetylation (Ace-H3K9 and Ace-H4K12) levels in Aβ-treated cells. The expression of TrkA was upregulated in HDAC1- or 3-silenced SH-SY5Y cells. However, there was no significant difference in TrkA expression between the HDAC2 knockdown and control cells. In conclusion, this study demonstrates that BHB protects against Aβ-induced neurotoxicity in SH-SY5Y cells. The underlying mechanism of the effect may be associated with the upregulation of TrkA expression by inhibiting HDAC1/3.

中文翻译：

---

β-羟基丁酸酯通过抑制SH-SY5Y细胞中的HDAC1 / 3来减轻Aβ诱导的TrkA表达下调。

酪氨酸激酶受体A（TrkA）在保护阿尔茨海默氏病（AD）中的胆碱能神经元中起重要作用。本研究旨在研究内源性组蛋白脱乙酰基酶（HDAC）抑制剂β-羟基丁酸酯（BHB）是否通过影响淀粉样β蛋白（Aβ）处理的SH-SY5Y细胞中的组蛋白乙酰化来上调TrkA的表达。结果表明，BHB改善了Aβ诱导的细胞活力降低和TrkA表达下调。此外，BHB抑制了Aβ处理的细胞中HDAC1 / 2/3表达的上调和组蛋白乙酰化（Ace-H3K9和Ace-H4K12）的下调。在HDAC1或3沉默的SH-SY5Y细胞中TrkA的表达上调。但是，在HDAC2敲低细胞和对照细胞之间，TrkA表达没有显着差异。总之，这项研究证明BHB可以抵抗SHβ-SY5Y细胞中Aβ诱导的神经毒性。该作用的潜在机制可能与通过抑制HDAC1 / 3导致TrkA表达上调有关。