Effects of regulation of the PI3K/AKT signaling pathway by TYROBP on neuroinflammation and autophagy / 中华老年医学杂志

ABSTRACT

Objective:To investigate the effects of TYRO protein tyrosine-binding protein(TYROBP)on neuroinflammation and autophagy via the PI3K/AKT signaling pathway in a transgenic APP/ PS1 mouse model of AD. Methods:C57BL/6J, TYROBP-/- and APP/ PS1 transgenic male mice aged 15-month-old were randomly divided into 3 group: the C57BL/6J group, the TYROBP-/- group and the APP/ PS1 group, with 19 in each group.The eight-arm maze test and novel object recognition test were conducted to assess the learning and memory ability of mice.The activation of microglia and NLRP3 inflammasomes were assessed by immunofluorescence.The mRNA levels of TNF-α, IL-6 and IL-1β were measured by real-time PCR, and the protein expression levels of NLRP3, cleaved caspase-1, SQSTM1, LC3B, TYROBP, p-PI3K, PI3K, p-AKT and AKT were assayed by Western blot. Results:Compared with the C57BL/6J group, the learning and memory abilities were significantly decreased(all P<0.05), activated microglia and NLRP3 inflammasomes were increased(all P<0.05), the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were increased(all P<0.05)and the protein expression levels of LC3B-Ⅱ, SQSTM1, TYROBP, p-PI3K, p-AKT were increased(all P<0.05)in the APP/ PS1 group.Compared with C57BL/6J group, the protein expression levels of TNF-α, IL-6, IL-1β, LC3B Ⅱ, SQSTM1, p-PI3K and p-AKT were decreased(all P<0.05). Conclusions:TYROBP promotes the inflammatory response and inhibits autophagy possibly by activating the PI3K/AKT signaling pathway, thus participating in the occurrence and development of AD.