A metabolic profile of polyamines in parkinson disease: A promising biomarker
A metabolic profile of polyamines in parkinson disease: A promising biomarker
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DOI：
10.1002/ana.25516
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发表时间：
2019-07-01
影响因子：
11.2
通讯作者：
Hattori, Nobutaka
中科院分区：
文献类型：
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作者：
Saiki, Shinji;Sasazawa, Yukiko;Hattori, Nobutaka
目的 衰老为帕金森病（PD）的最高风险因素。在生理条件下，亚精胺和精胺通过诱导自噬在实验中可延长寿命。因此，我们评估了每种多胺代谢物作为与年龄相关、具有诊断价值以及与疾病严重程度相关的PD生物标志物的能力。
方法 在队列A中对血浆进行全面代谢组分析（对照组，n = 45；PD组，n = 145），随后在队列B中分析7种多胺代谢物（对照组，n = 49；PD组，n = 186；进行性核上性麻痹，n = 19；阿尔茨海默病，n = 23）。此外，对队列B中连续接受检查的20例PD患者使用弥散张量成像（DTI）进行研究。根据Hoehn和Yahr分期（H&Y）以及统一帕金森病评定量表运动部分（UPDRS - III）评估每种多胺代谢物与疾病严重程度的相关性。另外，在多种细胞系中体外检测每种多胺代谢物的自噬诱导能力。
结果 在队列A中，N8 - 乙酰亚精胺和N - 乙酰腐胺水平在PD中分别显著且轻度升高。在队列B中，精胺水平以及精胺/亚精胺比值在PD中显著降低，同时伴有过度乙酰化。此外，N1,N8 - 二乙酰亚精胺水平具有最高的诊断价值，并与H&Y、UPDRS - III以及通过DTI量化的轴突退变相关。对照组中精胺/亚精胺比值随年龄下降，但在PD中持续受到抑制。在多胺代谢物中，精胺是最强的自噬诱导剂，尤其在SH - SY5Y细胞中。与对照组相比，未检测到5种编码与精胺/亚精胺代谢相关酶的基因存在显著遗传变异。
解读 精胺合成以及N1,N8 - 二乙酰亚精胺可能分别是对PD有用的诊断和与疾病严重程度相关的生物标志物。《神经病学年鉴》2019年
Objective Aging is the highest risk factor for Parkinson disease (PD). Under physiological conditions, spermidine and spermine experimentally enhance longevity via autophagy induction. Accordingly, we evaluated the ability of each polyamine metabolite to act as an age-related, diagnostic, and severity-associated PD biomarker. Methods Comprehensive metabolome analysis of plasma was performed in Cohort A (controls, n = 45; PD, n = 145), followed by analysis of 7 polyamine metabolites in Cohort B (controls, n = 49; PD, n = 186; progressive supranuclear palsy, n = 19; Alzheimer disease, n = 23). Furthermore, 20 patients with PD who were successively examined within Cohort B were studied using diffusion tensor imaging (DTI). Association of each polyamine metabolite with disease severity was assessed according to Hoehn and Yahr stage (H&Y) and Unified Parkinson's Disease Rating Scale motor section (UPDRS-III). Additionally, the autophagy induction ability of each polyamine metabolite was examined in vitro in various cell lines. Results In Cohort A, N8-acetylspermidine and N-acetylputrescine levels were significantly and mildly elevated in PD, respectively. In Cohort B, spermine levels and spermine/spermidine ratio were significantly reduced in PD, concomitant with hyperacetylation. Furthermore, N1,N8-diacetylspermidine levels had the highest diagnostic value, and correlated with H&Y, UPDRS-III, and axonal degeneration quantified by DTI. The spermine/spermidine ratio in controls declined with age, but was consistently suppressed in PD. Among polyamine metabolites, spermine was the strongest autophagy inducer, especially in SH-SY5Y cells. No significant genetic variations in 5 genes encoding enzymes associated with spermine/spermidine metabolism were detected compared with controls. Interpretation Spermine synthesis and N1,N8-diacetylspermidine may respectively be useful diagnostic and severity-associated biomarkers for PD. ANN NEUROL 2019