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[U-133,一种热休克蛋白诱导剂,可预防老年大鼠帕金森病临床前期模型中的睡眠障碍。]

[U-133, a heat shock proteins inducer, precludes sleep disturbances in a model of the preclinical stage of Parkinson's disease in aged rats.].

作者信息

Pastukhov Y F, Simonova V V, Shemyakova T S, Guzeev M A, Polonik S G, Ekimova I V

机构信息

I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, 44 pr. Toreza, St. Petersburg 194223, Russian Federation, e-mail:

G.B.Elyakov Pacific Institute of Bioorganic Chemistry, 159 str. 100-letyia Vladivostoka, Vladivostok 690022, Russian Federation.

出版信息

Adv Gerontol. 2019;32(6):935-940.

Abstract

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease, closely associated with aging. It is considered incurable due to both late diagnosis and symptomatic treatment, which is able to alter neither molecular mechanisms of sleep disruption nor the neurodegenerative processes, developing with aging and PD progression. In the present study, we assess the therapeutic potential of a novel chaperone inducer U-133 (acetyl 2,3,7-tris-O-glucoside echinochrome) in the preclinical stage of PD modelled in aged rats by the inhibition of the proteasomal system in the brain. U-133 is a derivative of the sea urchin pigment echinochrome (2,3,5,7,8-pentahydroxy-1,4-naphthoquinone) produced by glycosylation, which possesses neuroprotective, antioxidant, anticancer properties. The administration of U-133, inducing the synthesis of Hsp70i and Hdj1 heat shock proteins in the brain, precludes the increase of light sleep (drowsiness) stage and the decrease of deep slow-wave sleep total time, both occurring with the progression of the preclinical stage of PD modelled in aged Wistar rats. Deep slow-wave sleep is thought to promote glymphatic clearance and to accelerate protein synthesis. Thus, U-133-induced increase in deep slow-wave sleep percentage, as compared to the preclinical model, is considered having a neuroprotective effect that contributes to the intensification of the restorative function of neurons and counteracts the progressing neurodegeneration.

摘要

帕金森病(PD)是一种慢性进行性神经退行性疾病,与衰老密切相关。由于诊断较晚且采用对症治疗,而对症治疗既无法改变睡眠中断的分子机制,也无法改变随着衰老和帕金森病进展而发生的神经退行性过程,因此该病被认为无法治愈。在本研究中,我们通过抑制大脑中的蛋白酶体系统,评估了一种新型伴侣诱导剂U-133(乙酰基2,3,7-三-O-葡萄糖苷海胆色素)在老年大鼠帕金森病临床前模型中的治疗潜力。U-133是海胆色素(2,3,5,7,8-五羟基-1,4-萘醌)经糖基化产生的衍生物,具有神经保护、抗氧化、抗癌特性。给予U-133可诱导大脑中Hsp70i和Hdj1热休克蛋白的合成,可防止在老年Wistar大鼠帕金森病临床前模型进展过程中出现的浅睡眠(嗜睡)阶段增加和深度慢波睡眠总时间减少。深度慢波睡眠被认为可促进类淋巴系统清除并加速蛋白质合成。因此,与临床前模型相比,U-133诱导的深度慢波睡眠百分比增加被认为具有神经保护作用,有助于增强神经元的恢复功能并对抗进行性神经退行性变。

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