Endoplasmic reticulum(ER)stress can be caused by disturbances in the function of the ER with the accumulation of misfolded proteins.The ER response is characterized by unfolded protein response(UPR)causing translation...Endoplasmic reticulum(ER)stress can be caused by disturbances in the function of the ER with the accumulation of misfolded proteins.The ER response is characterized by unfolded protein response(UPR)causing translational attenuation,induction of ER chaperones and degradation of misfolded proteins.In case of prolonged or aggravated ER stress,cellular signals leading to apoptosis are activated.ER stress has been suggested to be involved in human neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis,as well as other disorders.Here we will discuss the neurotoxic effect of ER stress in these three major neurodegenerative diseases,and highlight current knowledge in this field that may reveal novel insight into disease mechanisms and help to design better therapies for these disorders.展开更多
文摘Endoplasmic reticulum(ER)stress can be caused by disturbances in the function of the ER with the accumulation of misfolded proteins.The ER response is characterized by unfolded protein response(UPR)causing translational attenuation,induction of ER chaperones and degradation of misfolded proteins.In case of prolonged or aggravated ER stress,cellular signals leading to apoptosis are activated.ER stress has been suggested to be involved in human neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis,as well as other disorders.Here we will discuss the neurotoxic effect of ER stress in these three major neurodegenerative diseases,and highlight current knowledge in this field that may reveal novel insight into disease mechanisms and help to design better therapies for these disorders.
文摘目的 评价神经变性疾病相关睡眠障碍的治疗方法及其疗效,为神经变性疾病相关睡眠障碍提供具有循证证据的最佳治疗方案。方法 分别以睡眠障碍(sleep disorder or sleep disturbance)、神经变性疾病(neurodegenerative diseases)、帕金森病(Parkinson's disease or PD)、阿尔茨海默病(Alzheimer's diseaseor AD)、多系统萎缩(multiple system atrophy or MSA)等中英文词组作为检索词,检索PubMed、美国国立医学图书馆(MEDLINE)、英国Cochrane图书馆、万方数据库和中国知识基础设施工程(CNKI)等数据库获取关于神经变性疾病相关睡眠障碍的系统评价、随机对照临床试验、临床对照试验、病例观察、流行病学调查研究等文献,采用Jadad量表对文献质量进行评价。结果 经筛选共纳入与神经变性疾病相关睡眠障碍治疗相关的英文文献35篇,包括系统评价2篇、随机对照临床试验5篇、临床对照试验13篇和病例观察13篇,余2篇为流行病学调查研究,与治疗无关。35篇文献中13篇被评为高质量文献,余22篇被评为低质量文献。经对各项临床试验治疗原则和不同治疗方法的治疗效果及安全性评价显示:(1)帕金森病相关睡眠障碍的治疗建议为注意睡眠卫生、合理应用拟多巴胺类药物,可改善失眠;亮光疗法可改善昼夜节律失调;氯硝西泮可改善快速眼动睡眠期行为障碍等。但迄今为止尚缺乏标准治疗方案,仍待更多的临床研究。(2)阿尔茨海默病相关睡眠障碍的治疗包括药物治疗和非药物治疗,其中药物治疗以褪黑素、乙酰胆碱酯酶抑制药、抗精神病药物、抗抑郁药物等为主;非药物治疗包括亮光疗法及行为疗法,但仍待更多的临床研究证明其疗效。(3)多系统萎缩相关睡眠障碍主要有睡眠相关呼吸障碍和快速眼动睡眠期行为障碍,睡眠相关呼吸障碍以经鼻持续气道正压通气为一线治疗方案,快速眼动睡眠期行为障碍首选氯硝西泮。(4)与睡眠障碍相关的其他神经系统变性疾病还有肌萎缩侧索硬化症、路易体痴呆等,但鲜有临床治疗的研究报道。结论 借助循证医学评价方法可为神经变性疾病相关睡眠障碍的循证治疗提供临床证据。
