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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.
Int J Mol Sci. 2019 Oct 03; 20(19)IJ

Abstract

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, Aβ 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.

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Authors+Show Affiliations

Haddad M
Institut National de Recherche Scientifique - Centre Armand-Frappier Santé Biotechnologie, Laval, QC H7V 1B7, Canada. Mohamed.Haddad@iaf.inrs.ca. Institute on Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada. Mohamed.Haddad@iaf.inrs.ca.
Perrotte M
Institut National de Recherche Scientifique - Centre Armand-Frappier Santé Biotechnologie, Laval, QC H7V 1B7, Canada. perrottemorgane@gmail.com. Institute on Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada. perrottemorgane@gmail.com.
Khedher MRB
Institut National de Recherche Scientifique - Centre Armand-Frappier Santé Biotechnologie, Laval, QC H7V 1B7, Canada. Mohamed.BenKheder@iaf.inrs.c. Institute on Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada. Mohamed.BenKheder@iaf.inrs.c.
Demongin C
Institut National de Recherche Scientifique - Centre Armand-Frappier Santé Biotechnologie, Laval, QC H7V 1B7, Canada. clement.demongin@laposte.net.
Lepage A
Department of Medicine, Geriatric Division, Research Center on Aging, Sherbrooke University, Sherbrooke, QC J1H 4C4, Canada. Aurelielepage18@gmail.com.
Fülöp T
Department of Medicine, Geriatric Division, Research Center on Aging, Sherbrooke University, Sherbrooke, QC J1H 4C4, Canada. Tamas.Fulop@USherbrooke.ca.
Ramassamy C
Institut National de Recherche Scientifique - Centre Armand-Frappier Santé Biotechnologie, Laval, QC H7V 1B7, Canada. Charles.Ramassamy@iaf.inrs.ca. Institute on Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada. Charles.Ramassamy@iaf.inrs.ca.

MeSH

AgedAlzheimer DiseaseBiomarkersBrain-Derived Neurotrophic FactorCell Line, TumorCognitive DysfunctionExtracellular VesiclesFemaleGlyoxalHumansInflammation MediatorsMaleNeuronsPyruvaldehydeROC CurveSeverity of Illness Index

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31623327

Citation

Haddad, Mohamed, et al. "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, 2019.
Haddad M, Perrotte M, Khedher MRB, et al. 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. Int J Mol Sci. 2019;20(19).
Haddad, M., Perrotte, M., Khedher, M. R. B., Demongin, C., Lepage, A., Fülöp, T., & Ramassamy, C. (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, 20(19). https://doi.org/10.3390/ijms20194906
Haddad M, et al. 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. Int J Mol Sci. 2019 Oct 3;20(19) PubMed PMID: 31623327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Haddad,Mohamed, AU - Perrotte,Morgane, AU - Khedher,Mohamed Raâfet Ben, AU - Demongin,Clément, AU - Lepage,Aurélie, AU - Fülöp,Tamás, AU - Ramassamy,Charles, Y1 - 2019/10/03/ PY - 2019/08/31/received PY - 2019/09/14/revised PY - 2019/09/23/accepted PY - 2019/10/19/entrez PY - 2019/10/19/pubmed PY - 2020/2/25/medline KW - Alzheimer’s disease KW - Growth KW - advanced glycation products KW - extracellular vesicles KW - inflammatory and vascular factors KW - mild cognitive impairment JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 19 N2 - 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, Aβ 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/31623327/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_ DB - PRIME DP - Unbound Medicine ER -