Neuroprotective Activities of Heparin, Heparinase III, and Hyaluronic Acid on the Aβ42-Treated Forebrain Spheroids Derived from Human Stem Cells,ACS Biomaterials Science & Engineering

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Neuroprotective Activities of Heparin, Heparinase III, and Hyaluronic Acid on the Aβ42-Treated Forebrain Spheroids Derived from Human Stem Cells
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2018-06-28 00:00:00 , DOI: 10.1021/acsbiomaterials.8b00021
Julie Bejoy ₁ , Liqing Song ₁ , Zhe Wang ₂ , Qing-Xiang Sang _{2,

3} , Yi Zhou ₄ , Yan Li _{1,

3}

Affiliation

Extracellular matrix (ECM) components of the brain play complex roles in neurodegenerative diseases. The study of microenvironment of brain tissues with Alzheimer’s disease revealed colocalized expression of different ECM molecules such as heparan sulfate proteoglycans (HSPGs), chondroitin sulfate proteoglycans (CSPGs), matrix metalloproteinases (MMPs), and hyaluronic acid. In this study, both cortical and hippocampal populations were generated from human-induced pluripotent stem cell-derived neural spheroids. The cultures were then treated with heparin (competes for Aβ affinity with HSPG), heparinase III (digests HSPGs), chondroitinase (digests CSPGs), hyaluronic acid, and an MMP-2/9 inhibitor (SB-3CT) together with amyloid β (Aβ42) oligomers. The results indicate that inhibition of HSPG binding to Aβ42 using either heparinase III or heparin reduces Aβ42 expression and increases the population of β-tubulin III⁺ neurons, whereas the inhibition of MMP2/9 induces more neurotoxicity. The results should enhance our understanding of the contribution of ECMs to the Aβ-related neural cell death.

中文翻译：

肝素、肝素酶 III 和透明质酸对经 Aβ42 处理的人干细胞来源的前脑球体的神经保护活性

大脑的细胞外基质（ECM）成分在神经退行性疾病中发挥着复杂的作用。对阿尔茨海默病脑组织微环境的研究揭示了不同 ECM 分子的共定位表达，例如硫酸乙酰肝素蛋白聚糖 (HSPG)、硫酸软骨素蛋白聚糖 (CSPG)、基质金属蛋白酶 (MMP) 和透明质酸。在这项研究中，皮质和海马群体都是由人类诱导的多能干细胞衍生的神经球体产生的。然后用肝素（与 HSPG 竞争 Aβ 亲和力）、肝素酶 III（消化 HSPG）、软骨素酶（消化 CSPG）、透明质酸、MMP-2/9 抑制剂 (SB-3CT) 以及淀粉样蛋白 β 处理培养物。 Aβ42) 寡聚物。结果表明，使用肝素酶 III 或肝素抑制 HSPG 与 Aβ42 的结合会降低 Aβ42 的表达并增加 β-微管蛋白 III ⁺神经元的数量，而抑制 MMP2/9 会诱导更多的神经毒性。这些结果应该增强我们对 ECM 对 Aβ 相关神经细胞死亡的贡献的理解。

更新日期：2018-06-28

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