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帕金森病中的蛋白质酶失调:来自血液分析的见解

Alfonso Di Costanzo^1,2, Carmela Fusco^1,3, Rosa Camerlingo⁴

¹Department of Medicine and Health Sciences, Centre for Research and Training in Medicine of Aging, University of Molise, 86100, Campobasso, Italy.

Molecular neurobiology

|December 23, 2025

概括

在帕金森病 (PD) 患者中,外围蛋白质酶活性,特别是PSMB5的调节失调,与疾病严重程度相关. 这表明PD进展的潜在外围生物标志物.

科学领域:

神经科学是一个神经科学.
生物化学生物化学
遗传学是一个遗传学.

背景情况:

帕金森病 (PD) 涉及α-synuclein聚合,线粒体功能障碍和蛋白质稳定性受损.
反映PD中这些细胞变化的外围生物标志物尚未得到很好的定义.
蛋白质稳定对于细胞健康至关重要,其破坏与神经退行性疾病有关.

研究的目的:

在PD患者的外周血液中评估乙烯酸皮水解酶 (APEH) 和蛋白酶子单元β型-5 (PSMB5) 的酶活性和基因表达.
为了将这些酶和基因表达发现与PD疾病严重程度相关联.
调查潜在的PD进展的外围生物标志物.

主要方法:

招募了13名PD患者和13名年龄匹配的健康对照 (HLT).
在全血,红细胞和免疫细胞部分中测量了APEH和PSMB5基米素类 (CT类) 活性.
对APEH,PSMB5和相关基因 (NAA10,ACY1,UBA1,UBE2I,PRKN,SNCA,PARK7,SOD2) 进行基因表达分析.

主要成果:

APEH活动在PD和HLT组之间没有显著差异.
PSMB5CT类活性在淋巴细胞中降低,但在PD患者的红细胞和全血中升高.
在PD患者中,PARK7基因表达显著下降;APEH和PSMB5表达保持不变. 蛋白质体变化与疾病严重程度和认知障碍相关.

结论:

在PD患者的外周血液中证明了区间特异性蛋白质体调节失调,表明系统性蛋白质稳定失衡.
观察到的蛋白质体活性变化与PD临床进展和严重程度相关.
外围蛋白质体活动概况可以作为跟踪PD进展的潜在生物标志物.

关键词:

亚佩赫 (APEH) 是一个神灵.PSMB5 PSMB5 在线播放帕金森病是帕金森氏症的一种疾病.周围血液中的生物标志物蛋白质体活动蛋白质体活动

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