Blood-Brain Barrier Permeable Chitosan Oligosaccharides Interfere with beta-Amyloid Aggregation and Alleviate beta-Amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of Polymerization-Dependent Manner
文献类型：期刊论文
| 作者 | Zhu, Limeng1,2; Li, Ruilian1,2; Jiao, Siming1; Wei, Jinhua1; Yan, Yalu1; Wang, Zhuo A.1; Li, Jianjun1; Du, Yuguang1 |
| 刊名 | MARINE DRUGS
 |
| 出版日期 | 2020-10-01 |
| 卷号 | 18期号:10页码:22 |
| 关键词 | Alzheimer’ s disease chitosan oligosaccharides blood-brain barrier Aβ 42 aggregation binding affinity cytotoxicity |
| DOI | 10.3390/md18100488 |
| 英文摘要 | It is proven that beta-amyloid (A beta) aggregates containing cross-beta-sheet structures led to oxidative stress, neuroinflammation, and neuronal loss via multiple pathways. Therefore, reduction of A beta neurotoxicity via inhibiting aggregation of A beta or dissociating toxic A beta aggregates into nontoxic forms might be effective therapeutic methods for Alzheimer's disease (AD) treatment. This study was designed to explore interference of chitosan oligosaccharides (COS) on beta-(1-42)-amyloid protein (A beta 42) aggregation and A beta 42-induced cytotoxicity. Here it was demonstrated that COS showed good blood-brain barrier (BBB) penetration ability in vitro and in vivo. The experimental results showed that COS efficiently interfered with A beta 42 aggregation in dose- and degree of polymerization (DP)-dependent manners, and COS monomer with DP6 showed the best effect on preventing conformational transition into beta-sheet-rich structures. Based on the binding affinity analysis by microscale thermophoresis (MST), it was confirmed that COS could directly bind with A beta 42 in a DP-dependent manner. Our findings demonstrated that different performance of COS monomers with different DPs against A beta 42 assembly was, to some extent, attributable to their different binding capacities with A beta 42. As a result, COS significantly ameliorated A beta 42-induced cytotoxicity. Taken together, our studies would point towards a potential role of COS in treatment of AD. |
| WOS关键词 | BIOLOGICAL-ACTIVITIES ; ALZHEIMERS ; CHITOOLIGOSACCHARIDES ; RECEPTOR ; OLIGOMERS ; PEPTIDE ; DISEASE |
| 资助项目 | National Natural Science Fund, China[U1608255] ; National Natural Science Fund, China[31700705] ; National Key Research and Development Program, China[2017YFD0502303-4] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | MDPI |
| WOS记录号 | WOS:000585114600001 |
| 资助机构 | National Natural Science Fund, China ; National Key Research and Development Program, China |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/42532]  |
| 专题 | 中国科学院过程工程研究所 |
| 通讯作者 | Wang, Zhuo A.; Li, Jianjun; Du, Yuguang |
| 作者单位 | 1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhu, Limeng,Li, Ruilian,Jiao, Siming,et al. Blood-Brain Barrier Permeable Chitosan Oligosaccharides Interfere with beta-Amyloid Aggregation and Alleviate beta-Amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of Polymerization-Dependent Manner[J]. MARINE DRUGS,2020,18(10):22. |
| APA | Zhu, Limeng.,Li, Ruilian.,Jiao, Siming.,Wei, Jinhua.,Yan, Yalu.,...&Du, Yuguang.(2020).Blood-Brain Barrier Permeable Chitosan Oligosaccharides Interfere with beta-Amyloid Aggregation and Alleviate beta-Amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of Polymerization-Dependent Manner.MARINE DRUGS,18(10),22. |
| MLA | Zhu, Limeng,et al."Blood-Brain Barrier Permeable Chitosan Oligosaccharides Interfere with beta-Amyloid Aggregation and Alleviate beta-Amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of Polymerization-Dependent Manner".MARINE DRUGS 18.10(2020):22. |
入库方式： OAI收割
来源：过程工程研究所
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