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首页> 外文期刊>Experimental Brain Research >Cathepsin S increases tau oligomer formation through limited cleavage, but only IL-6, not cathespin S serum levels correlate with disease severity in the neurodegenerative tauopathy progressive supranuclear palsy
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Cathepsin S increases tau oligomer formation through limited cleavage, but only IL-6, not cathespin S serum levels correlate with disease severity in the neurodegenerative tauopathy progressive supranuclear palsy

机译：组织蛋白酶通过有限的裂解增加了Tau寡聚物形成，但只有IL-6，而不是Cathespin的血清水平与神经变性疏松疏近的肺病变疾病的疾病严重程度相关

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摘要

Limited cleavage promotes the aggregation propensity of protein tau in neurodegenerative tauopathies. Cathepsin S (CatS) is overexpressed in brains of patients suffering from tauopathies such as Alzheimer's disease (AD). Furthermore, CatS serum levels correlate with survival in the elderly. The current study investigates whether limited cleavage by CatS promotes tau aggregation, and whether CatS serum levels may correlate with disease severity in tauopathies. Oligomer formation of fluorescently labeled protein tau was monitored by single particle fluorescence spectroscopy after coincubation with CatS. Tau cleavage patterns were investigated by SDS-PAGE. For serum analyses, samples were collected from 42 patients with probable progressive supranuclear palsy (PSP) according to NINDS-PSP criteria. Disease severity was assessed by PSP rating scale (PSP-RS), PSP staging system (PSP-S) and Schwab and England Activities of Daily Living (SEADL). CatS, cystatin C (CysC) and interleukin 6 (IL-6) serum levels were determined by ELISA, ECLIA and turbidimetry, respectively. SDS-PAGE demonstrated a distinct cleavage pattern of protein tau after coincubation with CatS. Furthermore, tau oligomer formation was increased 2.4-fold (p < 0.05) after limited cleavage. Serum CatS and CysC levels did not correlate with disease severity in PSP. Of note, IL-6 correlated with PSP-S (r = 0.41; 95% CI 0.11-0.65; p = 0.008), SEADL (r = -0.37; 95% CI -0.61 to -0.06; p = 0.017) and the history and gait/midline subdomains of the PSP-RS. While CatS facilitates tau aggregation in vitro, serum levels of CatS appear not to correlate with disease severity. The observed correlation of IL-6 with disease severity warrants further investigation of inflammatory markers in PSP.
机译：有限的裂解促进蛋白质Tau蛋白Tauopathies的聚集倾向。组织蛋白酶S（猫）在患有亚洲治疗症（AD）的患者的患者的大脑中过表达。此外，猫血清水平与老年人的存活率相关。目前的研究调查了猫的裂解是否有限促进TAU聚集，以及猫血清水平是否可能与薄膜缺陷的疾病严重程度相关。用肌肉凝结后单颗粒荧光光谱监测荧光标记的蛋白质的低聚物形成。通过SDS-PAGE研究了TAU裂解模式。对于血清分析，根据Ninds-PSP标准，从42例可能的渐进性上牙巴肌（PSP）收集样品。通过PSP评级规模（PSP-RS），PSP分期系统（PSP-S）和Schwab以及日常生活活动（SEADL）的活动评估疾病严重程度。通过ELISA，Eclia和Tymidetry测定猫，胱抑素C（Cysc）和白细胞介素6（IL-6）血清水平。 SDS-PAGE在用猫辛酸化后展示了蛋白质Tau的明显裂解模式。此外，在有限的切割后，Tau寡聚物形成增加了2.4倍（P <0.05）。血清猫和Cysc水平与PSP中的疾病严重程度无关。注意，IL-6与PSP-S相关（r = 0.41; 95％CI 0.11-0.65; p = 0.008），seadl（r = -0.37; 95％ci -0.61至-0.06; p = 0.017）和PSP-RS的历史和步态/中线子域。虽然猫在体外促进Tau聚集，但血清猫水平似乎与疾病严重程度不相关。观察到IL-6与疾病严重程度的相关性需要进一步调查PSP中炎症标志物。

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