Kynurenine pathway metabolites in cerebrospinal fluid and blood as potential biomarkers in Huntington's disease.
Kynurenine pathway metabolites in cerebrospinal fluid and blood as potential biomarkers in Huntington's disease.
复制标题
DOI：
10.1111/jnc.15360
复制
发表时间：
2021-07
影响因子：
4.7
通讯作者：
Wild EJ
中科院分区：
文献类型：
--
作者：
Rodrigues FB;Byrne LM;Lowe AJ;Tortelli R;Heins M;Flik G;Johnson EB;De Vita E;Scahill RI;Giorgini F;Wild EJ
来自几种模型和死后人脑组织研究的证据线的汇合支持犬尿氨酸途径（KP）参与亨廷顿病（HD）发病机制。定量HD生物流体中的KP代谢物是理想的，既可以研究病理生物学，也可以作为生物标志物的潜在来源，以定量途径功能障碍并评价靶向其组分的治疗干预的生化影响。在一项标准化收集脑脊液（CSF）、血液、表型和成像数据的前瞻性单中心对照队列研究中，我们使用高效液相色谱法测量了80名参与者（20名健康对照者、20名预显HD和40名显HD）CSF和血浆中KP代谢物-色氨酸、犬尿氨酸、犬尿烯酸、3-羟基犬尿氨酸、邻氨基苯甲酸和喹啉酸的水平。我们研究了短期稳定性、组间差异、与临床和影像学指标的相关性，并为未来研究计算了样本量。总体而言，CSF和血浆中的KP代谢物在6周内保持稳定，未显示显著的组间差异，且与临床或影像学指标无关。我们的结论是，研究的代谢物是容易和可靠的定量在两个生物流体中的控制和HD基因扩增载体。然而，我们发现几乎没有证据支持HD中KP的实质性紊乱，至少在患者源性生物液中代谢物水平反映的程度上。来自非人类模型的证据支持犬尿氨酸途径参与亨廷顿病。然而，在活人身上的证据是有限的。在一项标准化收集脑脊液和血液的前瞻性研究中，我们使用高效液相色谱法分析了这一途径。我们得出的结论是，所选代谢物易于可靠地定量。然而，我们发现很少有证据支持亨廷顿病中犬尿氨酸途径的实质性紊乱，至少在某种程度上，它反映了患者来源的生物液体中的代谢物水平。3-HK，3-羟基犬尿氨酸; KYNA，犬尿烯酸; QUIN，喹啉酸。
Converging lines of evidence from several models, and post‐mortem human brain tissue studies, support the involvement of the kynurenine pathway (KP) in Huntington's disease (HD) pathogenesis. Quantifying KP metabolites in HD biofluids is desirable, both to study pathobiology and as a potential source of biomarkers to quantify pathway dysfunction and evaluate the biochemical impact of therapeutic interventions targeting its components. In a prospective single‐site controlled cohort study with standardised collection of cerebrospinal fluid (CSF), blood, phenotypic and imaging data, we used high‐performance liquid‐chromatography to measure the levels of KP metabolites—tryptophan, kynurenine, kynurenic acid, 3‐hydroxykynurenine, anthranilic acid and quinolinic acid—in CSF and plasma of 80 participants (20 healthy controls, 20 premanifest HD and 40 manifest HD). We investigated short‐term stability, intergroup differences, associations with clinical and imaging measures and derived sample‐size calculation for future studies. Overall, KP metabolites in CSF and plasma were stable over 6 weeks, displayed no significant group differences and were not associated with clinical or imaging measures. We conclude that the studied metabolites are readily and reliably quantifiable in both biofluids in controls and HD gene expansion carriers. However, we found little evidence to support a substantial derangement of the KP in HD, at least to the extent that it is reflected by the levels of the metabolites in patient‐derived biofluids. Converging lines of evidence from non‐human models support the involvement of the kynurenine pathway in Huntington's disease. However, evidence in living humans is limited. In a prospective study with standardised collection of cerebrospinal fluid and blood, we used high‐performance liquid‐chromatography to analyse this pathway. We concluded that the selected metabolites are readily and reliably quantifiable. Yet, we found little evidence to support a substantial derangement of the kynurenine pathway in Huntington's disease, at least to the extent that it is reflected by the levels of the metabolites in patient‐derived biofluids. 3‐HK, 3‐hydroxykynurenine; KYNA, kynurenic acid; QUIN, quinolinic acid.
登录
查看更多内容
影响因子：
4.6
作者：
Byrne LM;Rodrigues FB;Johnson EB;De Vita E;Blennow K;Scahill R;Zetterberg H;Heslegrave A;Wild EJ
通讯作者：
Wild EJ
影响因子：
4.7
作者：
HIRAKU, Y;INOUE, S;KAWANISHI, S
通讯作者：
KAWANISHI, S
DOI：
10.1093/brain/awy122
发表时间：
2018-07-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Gregory S;Long JD;Klöppel S;Razi A;Scheller E;Minkova L;Johnson EB;Durr A;Roos RAC;Leavitt BR;Mills JA;Stout JC;Scahill RI;Tabrizi SJ;Rees G;Track-On investigators
通讯作者：
Track-On investigators
影响因子：
2.5
作者：
FOSTER, AC;VEZZANI, A;SCHWARCZ, R
通讯作者：
SCHWARCZ, R
影响因子：
14.5
作者：
HEYES, MP;SAITO, K;TOURTELLOTTE, WW
通讯作者：
TOURTELLOTTE, WW