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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
Zhu, Limeng1,2; Li, Ruilian1,2; Jiao, Siming1; Wei, Jinhua1; Yan, Yalu1; Wang, Zhuo A.1; Li, Jianjun1; Du, Yuguang1
2020-10-01
Source PublicationMARINE DRUGS
Volume18Issue:10Pages:22
AbstractIt 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.
KeywordAlzheimer’ s disease chitosan oligosaccharides blood-brain barrier 42 aggregation binding affinity cytotoxicity
DOI10.3390/md18100488
Language英语
WOS KeywordBIOLOGICAL-ACTIVITIES ; ALZHEIMERS ; CHITOOLIGOSACCHARIDES ; RECEPTOR ; OLIGOMERS ; PEPTIDE ; DISEASE
Funding ProjectNational Natural Science Fund, China[U1608255] ; National Natural Science Fund, China[31700705] ; National Key Research and Development Program, China[2017YFD0502303-4]
WOS Research AreaPharmacology & Pharmacy
WOS SubjectChemistry, Medicinal
Funding OrganizationNational Natural Science Fund, China ; National Key Research and Development Program, China
WOS IDWOS:000585114600001
PublisherMDPI
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/42533
Collection中国科学院过程工程研究所
Corresponding AuthorWang, Zhuo A.; Li, Jianjun; Du, Yuguang
Affiliation1.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
Recommended Citation
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.
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