Dataset Information

Blood-Brain Barrier Permeable Chitosan Oligosaccharides Interfere with ?-Amyloid Aggregation and Alleviate ?-Amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of Polymerization-Dependent Manner.

ABSTRACT: It is proven that ?-amyloid (A?) aggregates containing cross-?-sheet structures led to oxidative stress, neuroinflammation, and neuronal loss via multiple pathways. Therefore, reduction of A? neurotoxicity via inhibiting aggregation of A? or dissociating toxic A? 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 ?-(1-42)-amyloid protein (A?42) aggregation and A?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?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 ?-sheet-rich structures. Based on the binding affinity analysis by microscale thermophoresis (MST), it was confirmed that COS could directly bind with A?42 in a DP-dependent manner. Our findings demonstrated that different performance of COS monomers with different DPs against A?42 assembly was, to some extent, attributable to their different binding capacities with A?42. As a result, COS significantly ameliorated A?42-induced cytotoxicity. Taken together, our studies would point towards a potential role of COS in treatment of AD.

SUBMITTER: Zhu L

PROVIDER: S-EPMC7650801 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Blood-Brain Barrier Permeable Chitosan Oligosaccharides Interfere with β-Amyloid Aggregation and Alleviate β-Amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of Polymerization-Dependent Manner.

Zhu Limeng L Li Ruilian R Jiao Siming S Wei Jinhua J Yan Yalu Y Wang Zhuo A ZA Li Jianjun J Du Yuguang Y

Marine drugs 20200925 10

It is proven that β-amyloid (Aβ) aggregates containing cross-β-sheet structures led to oxidative stress, neuroinflammation, and neuronal loss via multiple pathways. Therefore, reduction of Aβ neurotoxicity via inhibiting aggregation of Aβ or dissociating toxic Aβ 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 β-(1-42)-amyloid protein (Aβ42) aggregat ...[more]

PMID: 32992800

Similar Datasets

Project description:BackgroundCellodextrin phosphorylase (CdP; EC 2.4.1.49) catalyzes the iterative β-1,4-glycosylation of cellobiose using α-D-glucose 1-phosphate as the donor substrate. Cello-oligosaccharides (COS) with a degree of polymerization (DP) of up to 6 are soluble while those of larger DP self-assemble into solid cellulose material. The soluble COS have attracted considerable attention for their use as dietary fibers that offer a selective prebiotic function. An efficient synthesis of soluble COS requires good control over the DP of the products formed. A mathematical model of the iterative enzymatic glycosylation would be important to facilitate target-oriented process development.ResultsA detailed time-course analysis of the formation of COS products from cellobiose (25 mM, 50 mM) and α-D-glucose 1-phosphate (10-100 mM) was performed using the CdP from Clostridium cellulosi. A mechanism-based, Michaelis-Menten type mathematical model was developed to describe the kinetics of the iterative enzymatic glycosylation of cellobiose. The mechanistic model was combined with an empirical description of the DP-dependent self-assembly of the COS into insoluble cellulose. The hybrid model thus obtained was used for kinetic parameter determination from time-course fits performed with constraints derived from initial rate data. The fitted hybrid model provided excellent description of the experimental dynamics of the COS in the DP range 3-6 and also accounted for the insoluble product formation. The hybrid model was suitable to disentangle the complex relationship between the process conditions used (i.e., substrate concentration, donor/acceptor ratio, reaction time) and the reaction output obtained (i.e., yield and composition of soluble COS). Model application to a window-of-operation analysis for the synthesis of soluble COS was demonstrated on the example of a COS mixture enriched in DP 4.ConclusionsThe hybrid model of CdP-catalyzed iterative glycosylation is an important engineering tool to study and optimize the biocatalytic synthesis of soluble COS. The kinetic modeling approach used here can be of a general interest to be applied to other iteratively catalyzed enzymatic reactions of synthetic importance.

Dataset Information

Blood-Brain Barrier Permeable Chitosan Oligosaccharides Interfere with ?-Amyloid Aggregation and Alleviate ?-Amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of Polymerization-Dependent Manner.

Publications

Blood-Brain Barrier Permeable Chitosan Oligosaccharides Interfere with β-Amyloid Aggregation and Alleviate β-Amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of Polymerization-Dependent Manner.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets