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Inhibition of MAPT enhances the effect of bexarotene and attenuates the damage after traumatic brain injury using in vivo and in vitro experiments
Folia Neuropathologica ( IF 1.5 ) Pub Date : 2020-10-21 , DOI: 10.5114/fn.2020.100068
Haihai Dong 1 , Haitao Wang 1 , Liang Wang 1
Affiliation  

Traumatic brain injury (TBI) is the leading cause of death and disability around the world in all age groups. The primary injury of TBI is exacerbated by secondary injury, leading to an increased inflammatory response, cell death and even impairment of neurological function. Bexarotene has been found to improve neurological function in mice in an ApoE-dependent manner, but the detailed mechanism is not fully clear. Upregulated expression of MAPT has been found in mouse models after TBI; therefore, we hypothesized that inhibition of MAPT might contribute to the effects of bexarotene treatment in TBI models. Herein, we found that inhibition of MAPT enhanced the effects of bexarotene in increasing cellular viability and restoring brain function, and expression of anti-oxidative and anti-apoptotic molecules were elevated in response to inhibition of MAPT. These effects might be mediated by activation of the Nrf2/HO-1 signalling pathway and inhibition of the MAPK/NF-kB signalling pathway. Thus, we concluded that inhibition of MAPT might represent a novel treatment target for TBI.

中文翻译:

使用体内外实验抑制 MAPT 增强贝沙罗汀的作用并减轻创伤性脑损伤后的损伤

创伤性脑损伤 (TBI) 是全世界所有年龄组死亡和残疾的主要原因。TBI 的原发性损伤因继发性损伤而加剧,导致炎症反应增加、细胞死亡甚至神经功能受损。已发现 Bexarotene 以 ApoE 依赖性方式改善小鼠的神经功能,但详细机制尚不完全清楚。在 TBI 后的小鼠模型中发现 MAPT 表达上调;因此,我们假设 MAPT 的抑制可能有助于贝沙罗汀治疗在 TBI 模型中的作用。在此,我们发现抑制 MAPT 增强了贝沙罗汀在增加细胞活力和恢复脑功能方面的作用,和抗氧化和抗凋亡分子的表达响应于 MAPT 的抑制而升高。这些效应可能是由激活 Nrf2/HO-1 信号通路和抑制 MAPK/NF-kB 信号通路介导的。因此,我们得出结论,MAPT 的抑制可能代表了 TBI 的新治疗目标。
更新日期:2020-10-30
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