Alleviating neuronal inflammation induced by Aß42 in SH-SY5Y through interaction with polysialic acid-oligomannuronate conjugate.
Int J Biol Macromol
; 276(Pt 1): 133862, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39013512
ABSTRACT
Amyloid beta (Aß) aggregation is one of the distinctive pathological hallmarks of Alzheimer's disease (AD). Therefore, the development of effective inhibitors against Aß aggregate formation offers great promise for the treatment of AD. In this study, we designed a novel negatively charged functionalized conjugate aimed at inhibiting Aß42 aggregation and attenuating neurotoxicity by grafting polysialic acid with mannuronate oligosaccharide, a biocompatible glycan extracted from seaweeds, designated as polysialic acid-mannan conjugate (PSA-MOS). ThT, biological microscopy, TEM and CD confirmed the inhibition of Aß42 aggregation by PSA-MOS, as well as its ability to inhibit the conformational transition of Aß42 to ß-sheet. CCK-8 assay demonstrated that PSA-MOS was not cytotoxic to SH-SY5Y (p < 0.05) and promoted cell proliferation. In the Aß42-induced SH-SY5Y injury models, PSA-MOS dose-dependently ameliorated cytotoxicity (p < 0.0001) and significantly reduced the levels of inflammatory factors of IL-1ß (p < 0.0001), IL-6 (p < 0.0001) and TNF-α (p < 0.05). MD simulations demonstrated that PSA-MOS effectively impeded the α-helix to ß-sheet transition of the Aß42 monomer via electrostatic interactions with its CTR and NTR regions. These findings demonstrate the therapeutic potential of PSA-MOS as promising glycoconjugate for the treatment of AD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sialic Acids
/
Amyloid beta-Peptides
/
Inflammation
Limits:
Humans
Language:
En
Journal:
Int J Biol Macromol
/
Int. j. biol. macromol
/
International journal of biological macromolecules
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Países Bajos