Astrocyte-specific glutamate transporter subtype 1 (GLT-1) plays an important role in influencing glutamate excitatory toxicity and preventing the death of excitatory toxic neurons. Although the mammalian target of rapamycin (mTOR)/protein kinase B(Akt)/nuclear factor kappa B signaling cascade is involved in the upregulation of astrocytic GLT-1 in oxygen–glucose deprivation (OGD), it is unclear whether the mTOR/Akt pathway is involved in astrocytic GLT-1 upregulation in OGD and reoxygenation (OGD/R). In this study, we found that the treatment of cultured astrocytes with rapamycin and triciribine led to the decreased astrocytes’ protrusions, smaller nuclei, and an increased apoptotic rate. The inhibitors of mTOR complex 1 significantly increased the expression levels of phosphorylated Akt-Ser473 (p-Akt), phosphorylated Akt-Thr308(p-Akt), and GLT-1, while Akt-specific inhibitors blocked GLT-1 expression, suggesting that the mTOR/Akt pathway is involved in GLT-1 upregulation. We further demonstrated that astrocytes under OGD/R adapted to environmental changes through the mTOR/Akt pathway, mainly by altering cell morphology and apoptosis and upregulating the expression levels of p-Akt and GLT-1. Our results suggested that astrocytes may adapt to short-term ischemic–reperfusion injury by regulating cell morphology, apoptosis and GLT-1 upregulation.

阿尔茨海默病(Alzheimer's disease,AD)是最常见的神经退行性疾病,AD的病理蛋白主要包括β-淀粉样蛋白(Aβ)和Tau,了解Aβ的生成和清除途径对于延缓甚至阻止AD是至关重要的.由于目前尚无有效干预手段,处于研究中的治疗方法 非常多,针对Aβ的研究最为热门,本文将阐述Aβ生成及代谢,介绍目前关于Aβ的治疗方法 的研究,分析通过促进外周代谢途径来减少脑中Aβ的浓度的治疗方法 ,为AD的治疗提供新思路.

Alzheimer's disease (AD) is a chronic neurodegenerative disease categorized by the deficiency in the cognition and memory. The present exploration was designed to unveil the ameliorative properties of ursolic acid (UA) against the aluminium chloride (AlCl3)-provoked AD in animals via the suppression of oxidative stress and neuroinflammation. Rats were used as follows: control group, UA control, AD control by AlCl3, UA + AD-induced rats. In the present study, we focused that the Behavioural (Morris water maze test and rotarod performance) brain biochemical parameters (acetylcholinesterase in hippocampus (AChE), aluminium content in hippocampus, cortex of catalase, superoxide dismutase (SOD) and reduced glutathione (GSH) were assessed to correlate the cognitive function with cholinergic transmission, oxidative stress and mRNA expression of inflammatory genes. This study indicated that AD-induced rats exhibited reduction in behavior, Rotarod and T-Maze tests, significantly reduced the antioxidant status, reduction in AchE, increased aluminium level and inflammatory gene expression. While rats treated with UA in protective effect exhibited significant improvement in behavior, Rotarod and T-Maze, antioxidants status, significant decrease in AchE, aluminium content and inflammatory gene expression. Furthermore, AD-induced our findings recommended that the UA treatment could ameliorate the cognitive impairment, suppress the neuroinflammation and oxi-dative stress in the AD animals.

铁自噬(ferritinophagy)是一种调节细胞内铁代谢的选择性自噬,由核受体共激活因子4(NCOA4)介导细胞内铁蛋白转运到自噬溶酶体中降解释放出游离铁,用于多种铁依赖的生理过程.正常生理情况下铁自噬维持着细胞内铁元素的平衡.当铁自噬过度激活时,细胞内过量的铁沉积诱导谷胱甘肽(GS H)耗竭以及谷胱甘肽过氧化物酶4(GPX4)的表达减少,导致细胞膜结构崩溃和破裂,最终引起细胞的铁死亡(ferroptosis).已有研究表明,氧化应激、炎症、兴奋性毒素和凋亡在中枢神经系统损伤的病理生理过程中起着重要作用.近年来,对铁死亡这一以铁依赖性脂质过氧化积累为特征的调节性细胞死亡与中枢神经系统疾病的关系研究越来越多.本文就铁自噬与铁死亡在中枢神经系统疾病中的作用研究进展进行综述.