摘要
背景:靶向淀粉样β42(Aβ42)寡聚体的治疗方法可能代表了用于预防和治疗阿尔茨海默病(AD)的有前景的神经保护策略。 目的:在这项研究中,我们评估了菠萝蛋白酶(一种源自菠萝茎的植物半胱氨酸蛋白酶)与合成的Aβ42单体和寡聚体相互作用的能力。我们还研究了菠萝蛋白酶在阿尔茨海默病脑脊液(CSF)中合成的Aβ42聚集体以及受其他神经疾病影响的对照患者体外干扰的能力。 方法:将合成单体和Aβ42聚集体在不同浓度菠萝蛋白酶的CSF中孵育。通过使用特异性单克隆抗体4G8的Western印迹分析来评估消化的效果以鉴定Aβ42的残留含量的模式。我们进一步使用大鼠原代皮层培养神经元(CN)来检查这种天然化合物的细胞毒性作用。 结果:我们发现菠萝蛋白酶成功降解Aβ42单体和低分子量和高分子量低聚物。事实上,当将3和6mU的菠萝蛋白酶制剂加入到CSF中时,与没有菠萝蛋白酶的在CSF中孵育的相同标准Aβ42制剂相比,Aβ42单体和寡聚物的残留量显着降低。此外,与载体处理的细胞相比,0.1,0.5和1mU / ml的菠萝蛋白酶孵育对CN无毒。 结论:总体而言,这些结果代表了菠萝蛋白酶对Aβ42寡聚体作用的重要见解,表明其可用于治疗AD。
关键词: 淀粉样β42,聚集,菠萝蛋白酶,阿尔茨海默病,AD治疗,预防。
Current Alzheimer Research
Title:Bromelain Degrades Aβ1-42 Monomers and Soluble Aggregates: An In Vitro Study in Cerebrospinal Fluid of Alzheimer’s Disease Patients
Volume: 15 Issue: 7
关键词: 淀粉样β42,聚集,菠萝蛋白酶,阿尔茨海默病,AD治疗,预防。
摘要: Background: Therapeutic approaches targeting amyloid β42 (Aβ42) oligomers may represent a promising neuroprotective strategy for the prevention and treatment of Alzheimer's disease (AD).
Objective: In this study we evaluated the ability of bromelain, a plant cysteine protease derived from pineapple stems, to interact with synthetic Aβ42 monomers and oligomers. We also examined the ability of bromelain to interfere in vitro with synthetic Aβ42 aggregates in the cerebrospinal fluid (CSF) of Alzheimer's disease as well as of control patients affected by other neurological diseases.
Method: Both synthetic monomers and aggregates of Aβ42 were incubated in CSF with varying concentrations of bromelain. The effects of digestion were evaluated by Western Blot analysis using the specific monoclonal antibody 4G8 to identify the patterns of residual content of Aβ42. We further used rat primary cortical culture neurons (CN) to examine the cytotoxic action of this natural compound.
Results: We found that bromelain successfully degraded Aβ42 monomers and low and high molecular weight oligomers. Indeed, when bromelain preparations of 3 and 6 mU were added to the CSF, the residual amount of Aβ42 monomers and oligomers were significantly reduced when compared to the same standard Aβ42 preparations incubated in CSF without bromelain. Moreover, bromelain incubations of 0.1, 0.5, and 1 mU/ml were not toxic to CN, as compared to vehicle treated cells.
Conclusion: Overall, these results represent an important insight into the action of bromelain on Aβ42 oligomers, suggesting its potential use in the therapy of AD.
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Bromelain Degrades Aβ1-42 Monomers and Soluble Aggregates: An In Vitro Study in Cerebrospinal Fluid of Alzheimer’s Disease Patients, Current Alzheimer Research 2018; 15 (7) . https://dx.doi.org/10.2174/1567205015666180123124851
DOI https://dx.doi.org/10.2174/1567205015666180123124851 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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