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PTPRD 是否可以作为治疗不宁腿综合征的潜在可用药靶标?

PTPRD as a candidate druggable target for therapies for restless legs syndrome?

机构信息

Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, Brazil.

Faculdade de Educação Física, Universidade Estadual de Campinas, Campinas, Brazil.

出版信息

J Sleep Res. 2021 Aug;30(4):e13216. doi: 10.1111/jsr.13216. Epub 2020 Oct 27.

Abstract

The gene that encodes the protein tyrosine phosphatase D (PTPRD) may be related to brain circuits associated with sleep, and has been seen as an interesting molecule, a "druggable" drug target. This gene is a potential candidate for increasing therapeutic advances in restless legs syndrome, a sleep-related movement disorder, that manifests as an uncontrollable desire to move limbs (legs) to relieve uncomfortable sensations. Changes in the PTPRD gene expression may increase the chance of developing this syndrome. Treatment with pramipexole is used in restless legs syndrome. This study aims to verify the effect of treatment with pramipexole on the PTPRD expression, as well as on the sleep pattern in an animal model for restless legs syndrome. For this, an animal model of sleep-related movement disorders (spontaneously hypertensive rats) was distributed in groups: (a) spontaneously hypertensive rats-control; (b) spontaneously hypertensive rats-pramipexole (0.125 mg kg for 4 weeks). The analyses of PTPRD gene and protein expression were performed in the striatum and spinal cord by quantitative real-time polymerase chain reaction and indirect enzyme-linked immunosorbent assay, respectively. Electrocorticographic and electromyographic analyses were performed. There was no difference in the PTPRD mRNA levels, as well as in the protein levels, although a tendency has been observed for decreased gene expression in the striatum and increased protein expression in the spinal cord in the spontaneously hypertensive rats-pramipexole group. Pramipexole improved the animals' sleep pattern. Thus, the treatment with pramipexole in the evaluated dose and time tended to alter the expression of the PTPRD protein in the spinal cord, in addition to significantly improving the sleep pattern.

摘要

编码蛋白酪氨酸磷酸酶 D(PTPRD)的基因可能与睡眠相关的大脑回路有关,并且已被视为一种有趣的分子,一种“可成药”的药物靶点。该基因是治疗不宁腿综合征(一种与睡眠相关的运动障碍,表现为不可控制地想要移动四肢(腿部)以缓解不适感觉)的潜在候选基因。PTPRD 基因表达的变化可能会增加发生这种综合征的机会。普拉克索用于治疗不宁腿综合征。本研究旨在验证普拉克索治疗对不宁腿综合征动物模型中 PTPRD 表达以及睡眠模式的影响。为此,将睡眠相关运动障碍动物模型(自发性高血压大鼠)分为以下几组:(a)自发性高血压大鼠对照组;(b)自发性高血压大鼠-普拉克索组(0.125mg/kg,连续 4 周)。通过定量实时聚合酶链反应和间接酶联免疫吸附试验分别对纹状体和脊髓中的 PTPRD 基因和蛋白表达进行分析。进行脑电和肌电图分析。PTPRD mRNA 水平以及蛋白水平均无差异,但自发性高血压大鼠-普拉克索组中纹状体的基因表达有降低趋势,脊髓的蛋白表达有增加趋势。普拉克索改善了动物的睡眠模式。因此,在评估的剂量和时间内,普拉克索治疗可能会改变脊髓中 PTPRD 蛋白的表达,同时显著改善睡眠模式。

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