5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro.
5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro.
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5-羟基环青霉素在体外抑制 β-淀粉样蛋白寡聚化并产生抗 β-淀粉样蛋白神经保护作用
DOI：
10.3390/molecules22101651
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发表时间：
2017-10-01
期刊：
影响因子：
--
通讯作者：
Cui W
中科院分区：
文献类型：
--
作者：
Zhao J;Liu F;Huang C;Shentu J;Wang M;Sun C;Chen L;Yan S;Fang F;Wang Y;Xu S;Naman CB;Wang Q;He S;Cui W
β-淀粉样蛋白 (Aβ) 寡聚物被认为是阿尔茨海默病 (AD) 的主要神经毒素。因此，抑制Aβ寡聚体的形成可能成为AD治疗的目标。在本研究中，借助斑点印迹分析和透射电子显微镜，发现最近从海绵相关真菌中分离出的环戊烯酮5-羟基环青霉素在体外能有效减少Aβ肽形成Aβ寡聚体。分子动力学模拟表明5-羟基环青霉素和Aβ肽之间存在疏水相互作用，这可能阻止Aβ肽的构象转变和寡聚化。此外，与正常的 Aβ 寡聚物相比，与 5-羟基环青霉素预孵育的 Aβ 寡聚物在添加到神经元 SH-SY5Y 细胞中时毒性更小。尽管目前形式的 5-羟基环青霉素在大脑中不具有生物利用度，但对该化学物质的进一步修饰或封装可能会提高 5-羟基环青霉素进入大脑的渗透性。基于目前的研究结果和5-羟基环青霉素的抗氧化应激特性，表明5-羟基环青霉素可能具有治疗AD的潜在疗效。
The oligomer of β-amyloid (Aβ) is considered the main neurotoxin in Alzheimer’s disease (AD). Therefore, the inhibition of the formation of Aβ oligomer could be a target for AD therapy. In this study, with the help of the dot blotting assay and transmission electronic microscopy, it was have discovered that 5-hydroxycyclopenicillone, a cyclopentenone recently isolated from a sponge-associated fungus, effectively reduced the formation of Aβ oligomer from Aβ peptide in vitro. Molecular dynamics simulations suggested hydrophobic interactions between 5-hydroxycyclopenicillone and Aβ peptide, which might prevent the conformational transition and oligomerization of Aβ peptide. Moreover, Aβ oligomer pre-incubated with 5-hydroxycyclopenicillone was less toxic when added to neuronal SH-SY5Y cells compared to the normal Aβ oligomer. Although 5-hydroxycyclopenicillone is not bioavailable in the brain in its current form, further modification or encapsulation of this chemical might improve the penetration of 5-hydroxycyclopenicillone into the brain. Based on the current findings and the anti-oxidative stress properties of 5-hydroxycyclopenicillone, it is suggested that 5-hydroxycyclopenicillone may have potential therapeutic efficacy in treating AD.
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5-羟基环青霉素，一种来自海绵衍生真菌木霉 HPQJ-34 的新型 β-淀粉样纤维化抑制剂
影响因子：
5.4
作者：
Fang F;Zhao J;Ding L;Huang C;Naman CB;He S;Wu B;Zhu P;Luo Q;Gerwick WH;Yan X;Wang Q;Zhang Z;Cui W
通讯作者：
Cui W
影响因子：
5.4
作者：
Indraningrat AA;Smidt H;Sipkema D
通讯作者：
Sipkema D
影响因子：
3.2
作者：
Tomaselli, S;Esposito, V;Picone, D
通讯作者：
Picone, D
DOI：
10.1073/pnas.1206433109
发表时间：
2012-07-31
影响因子：
11.1
作者：
Morgado, Isabel;Wieligmann, Karin;Faendrich, Marcus
通讯作者：
Faendrich, Marcus
DOI：
10.3390/molecules22071037
发表时间：
2017-06-23
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Ruiz-Torres V;Encinar JA;Herranz-López M;Pérez-Sánchez A;Galiano V;Barrajón-Catalán E;Micol V
通讯作者：
Micol V