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Methylglyoxal and Glyoxal as Potential Peripheral Markers for MCI Diagnosis and Their Effects on the Expression of Neurotrophic, Inflammatory and Neurodegenerative Factors in Neurons and in Neuronal Derived-Extracellular Vesicles

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Haddad, Mohamed, Perrotte, Morgane, ben Khedher, Mohamed Raâfet, Demongin, Clément, Lepage, Aurélie, Fulop, Tamas et Ramassamy, Charles ORCID: https://orcid.org/0000-0002-3252-5878 (2019). Methylglyoxal and Glyoxal as Potential Peripheral Markers for MCI Diagnosis and Their Effects on the Expression of Neurotrophic, Inflammatory and Neurodegenerative Factors in Neurons and in Neuronal Derived-Extracellular Vesicles International Journal of Molecular Sciences , vol. 20 , nº 19:4906. p. 1-19. DOI: 10.3390/ijms20194906.

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Résumé

Methylglyoxal (MG) and glyoxal (GO) are suggested to be associated with the development of neurodegenerative pathologies. However, their peripheral levels in relation to cognitive decline and their effects on key factors in neuronal cells are poorly investigated. The aim of this study was to determine their serum levels in MCI (mild cognitive impairment) and Alzheimer's disease (AD) patients, to analyze their effects on the neurotrophic and inflammatory factors, on neurodegenerative markers in neuronal cells and in neuronal derived-extracellular vesicles (nEVs). Our results show that MG and GO levels in serum, determined by HPLC, were higher in MCI. ROC (receiver-operating characteristic curves) analysis showed that the levels of MG in serum have higher sensitivity to differentiate MCI from controls but not from AD. Meanwhile, serum GO levels differentiate MCI from control and AD groups. Cells and nEVs levels of BDNF, PRGN, NSE, APP, MMP-9, ANGPTL-4, LCN2, PTX2, S100B, RAGE, Abeta peptide, pTau T181 and alpha-synuclein were quantified by luminex assay. Treatment of neuronal cells with MG or GO reduced the cellular levels of NSE, PRGN, APP, MMP-9 and ANGPTL-4 and the nEVs levels of BDNF, PRGN and LCN2. Our findings suggest that targeting MG and GO may be a promising therapeutic strategy to prevent or delay the progression of AD.

Type de document: Article
Mots-clés libres: Alzheimer’s disease; Growth; advanced glycation products; extracellular vesicles; inflammatory and vascular factors; mild cognitive impairment
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 22 juill. 2021 22:05
Dernière modification: 15 févr. 2022 21:24
URI: https://espace.inrs.ca/id/eprint/11598

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