Microglial AGE-albumin is critical for neuronal death in Parkinson’s disease: a possible implication for theranostics
Identifieur interne : 000284 ( Main/Exploration ); précédent : 000283; suivant : 000285Microglial AGE-albumin is critical for neuronal death in Parkinson’s disease: a possible implication for theranostics
Auteurs : Enkhjargal Bayarsaikhan [Corée du Sud, Mongolie] ; Delger Bayarsaikhan [Corée du Sud] ; Jaesuk Lee [Corée du Sud] ; Myeongjoo Son [Corée du Sud] ; Seyeon Oh [Corée du Sud] ; Jeongsik Moon [Corée du Sud] ; Hye-Jeong Park [Corée du Sud] ; Arivazhagan Roshini [Corée du Sud] ; Seung U. Kim [Canada] ; Byoung-Joon Song [États-Unis] ; Seung-Mook Jo [Corée du Sud] ; Kyunghee Byun [Corée du Sud] ; Bonghee Lee [Corée du Sud]Source :
- International Journal of Nanomedicine [ 1176-9114 ] ; 2016.
English descriptors
- KwdEn :
- Advanced Glycosylation End Product-Specific Receptor (metabolism), Animals, Apoptosis (drug effects), Blotting, Western, Brain (drug effects), Brain (metabolism), Brain (pathology), Case-Control Studies, Dopaminergic Neurons (drug effects), Dopaminergic Neurons (metabolism), Dopaminergic Neurons (pathology), Enzyme-Linked Immunosorbent Assay, Glycosylation End Products, Advanced (pharmacology), Humans, Immunoprecipitation, In Situ Nick-End Labeling, Mice, Microglia (drug effects), Microglia (pathology), Parkinson Disease (drug therapy), Parkinson Disease (metabolism), Parkinson Disease (pathology), Serum Albumin, Bovine (pharmacology), Theranostic Nanomedicine.
- MESH :
- chemical , metabolism : Advanced Glycosylation End Product-Specific Receptor.
- drug effects : Apoptosis, Brain, Dopaminergic Neurons, Microglia.
- drug therapy : Parkinson Disease.
- metabolism : Brain, Dopaminergic Neurons, Parkinson Disease.
- pathology : Brain, Dopaminergic Neurons, Microglia, Parkinson Disease.
- chemical , pharmacology : Glycosylation End Products, Advanced, Serum Albumin, Bovine.
- Animals, Blotting, Western, Case-Control Studies, Enzyme-Linked Immunosorbent Assay, Humans, Immunoprecipitation, In Situ Nick-End Labeling, Mice, Theranostic Nanomedicine.
Abstract
Advanced glycation end products (AGEs) are known to play an important role in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD), by inducing protein aggregation and cross-link, formation of Lewy body, and neuronal death. In this study, we observed that AGE-albumin, the most abundant AGE product in the human PD brain, is synthesized in activated microglial cells and accumulates in the extracellular space. AGE-albumin synthesis in human-activated microglial cells is distinctly inhibited by ascorbic acid and cytochalasin treatment. Accumulated AGE-albumin upregulates the receptor to AGE, leading to apoptosis of human primary dopamine (DA) neurons. In animal experiments, we observed reduced DA neuronal cell death by treatment with soluble receptor to AGE. Our study provides evidence that activated microglial cells are one of the main contributors in AGE-albumin accumulation, deleterious to DA neurons in human and animal PD brains. Finally, activated microglial AGE-albumin could be used as a diagnostic and therapeutic biomarker with high sensitivity for neurodegenerative disorders, including PD.
Url:
DOI: 10.2147/IJN.S95077
PubMed: 27601894
PubMed Central: 5003553
Affiliations:
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and Cell Biology, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Oh, Seyeon" sort="Oh, Seyeon" uniqKey="Oh S" first="Seyeon" last="Oh">Seyeon Oh</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Moon, Jeongsik" sort="Moon, Jeongsik" uniqKey="Moon J" first="Jeongsik" 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Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijn-10-281">Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Bonghee" sort="Lee, Bonghee" uniqKey="Lee B" first="Bonghee" last="Lee">Bonghee Lee</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya 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Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ijn-10-281">Department of General Laboratory, National Cancer Center of Mongolia, Ulaanbaatar, Mongolia</nlm:aff><country xml:lang="fr">Mongolie</country><wicri:regionArea>Department of General Laboratory, National Cancer Center of Mongolia, Ulaanbaatar</wicri:regionArea><wicri:noRegion>Ulaanbaatar</wicri:noRegion></affiliation></author><author><name sortKey="Bayarsaikhan, Delger" sort="Bayarsaikhan, Delger" uniqKey="Bayarsaikhan D" first="Delger" last="Bayarsaikhan">Delger Bayarsaikhan</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Jaesuk" sort="Lee, Jaesuk" uniqKey="Lee J" first="Jaesuk" last="Lee">Jaesuk Lee</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Son, Myeongjoo" sort="Son, Myeongjoo" uniqKey="Son M" first="Myeongjoo" last="Son">Myeongjoo Son</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijn-10-281">Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Oh, Seyeon" sort="Oh, Seyeon" uniqKey="Oh S" first="Seyeon" last="Oh">Seyeon Oh</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Moon, Jeongsik" sort="Moon, Jeongsik" uniqKey="Moon J" first="Jeongsik" last="Moon">Jeongsik Moon</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Park, Hye Jeong" sort="Park, Hye Jeong" uniqKey="Park H" first="Hye-Jeong" last="Park">Hye-Jeong Park</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Roshini, Arivazhagan" sort="Roshini, Arivazhagan" uniqKey="Roshini A" first="Arivazhagan" last="Roshini">Arivazhagan Roshini</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U" last="Kim">Seung U. Kim</name><affiliation wicri:level="1"><nlm:aff id="af4-ijn-10-281">Department of Medicine, University of British Columbia, Vancouver, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, University of British Columbia, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation></author><author><name sortKey="Song, Byoung Joon" sort="Song, Byoung Joon" uniqKey="Song B" first="Byoung-Joon" last="Song">Byoung-Joon Song</name><affiliation wicri:level="1"><nlm:aff id="af5-ijn-10-281">Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD</wicri:regionArea><wicri:noRegion>MD</wicri:noRegion></affiliation></author><author><name sortKey="Jo, Seung Mook" sort="Jo, Seung Mook" uniqKey="Jo S" first="Seung-Mook" last="Jo">Seung-Mook Jo</name><affiliation wicri:level="1"><nlm:aff id="af6-ijn-10-281">Department of Emergency Medical Services, Eulji University, Seongnam-si, Gyeonggi-do, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Emergency Medical Services, Eulji University, Seongnam-si, Gyeonggi-do</wicri:regionArea><wicri:noRegion>Gyeonggi-do</wicri:noRegion></affiliation></author><author><name sortKey="Byun, Kyunghee" sort="Byun, Kyunghee" uniqKey="Byun K" first="Kyunghee" last="Byun">Kyunghee Byun</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijn-10-281">Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Bonghee" sort="Lee, Bonghee" uniqKey="Lee B" first="Bonghee" last="Lee">Bonghee Lee</name><affiliation wicri:level="1"><nlm:aff id="af1-ijn-10-281">Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Center for Regenerative Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ijn-10-281">Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Anatomy and Cell Biology, Graduate School of Medicine, Gachon University, Incheon</wicri:regionArea><wicri:noRegion>Incheon</wicri:noRegion></affiliation></author></analytic><series><title level="j">International Journal of Nanomedicine</title><idno type="ISSN">1176-9114</idno><idno type="eISSN">1178-2013</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Advanced Glycosylation End Product-Specific Receptor (metabolism)</term><term>Animals</term><term>Apoptosis (drug effects)</term><term>Blotting, Western</term><term>Brain (drug effects)</term><term>Brain (metabolism)</term><term>Brain (pathology)</term><term>Case-Control Studies</term><term>Dopaminergic Neurons (drug effects)</term><term>Dopaminergic Neurons (metabolism)</term><term>Dopaminergic Neurons (pathology)</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Glycosylation End Products, Advanced (pharmacology)</term><term>Humans</term><term>Immunoprecipitation</term><term>In Situ Nick-End Labeling</term><term>Mice</term><term>Microglia (drug effects)</term><term>Microglia (pathology)</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (pathology)</term><term>Serum Albumin, Bovine (pharmacology)</term><term>Theranostic Nanomedicine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Advanced Glycosylation End Product-Specific Receptor</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Brain</term><term>Dopaminergic Neurons</term><term>Microglia</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Dopaminergic Neurons</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term><term>Dopaminergic Neurons</term><term>Microglia</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Glycosylation End Products, Advanced</term><term>Serum Albumin, Bovine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blotting, Western</term><term>Case-Control Studies</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Humans</term><term>Immunoprecipitation</term><term>In Situ Nick-End Labeling</term><term>Mice</term><term>Theranostic Nanomedicine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Advanced glycation end products (AGEs) are known to play an important role in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD), by inducing protein aggregation and cross-link, formation of Lewy body, and neuronal death. In this study, we observed that AGE-albumin, the most abundant AGE product in the human PD brain, is synthesized in activated microglial cells and accumulates in the extracellular space. AGE-albumin synthesis in human-activated microglial cells is distinctly inhibited by ascorbic acid and cytochalasin treatment. Accumulated AGE-albumin upregulates the receptor to AGE, leading to apoptosis of human primary dopamine (DA) neurons. In animal experiments, we observed reduced DA neuronal cell death by treatment with soluble receptor to AGE. Our study provides evidence that activated microglial cells are one of the main contributors in AGE-albumin accumulation, deleterious to DA neurons in human and animal PD brains. Finally, activated microglial AGE-albumin could be used as a diagnostic and therapeutic biomarker with high sensitivity for neurodegenerative disorders, including PD.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Poirier, J" uniqKey="Poirier J">J Poirier</name></author><author><name sortKey="Kogan, S" uniqKey="Kogan S">S Kogan</name></author><author><name sortKey="Gauthier, S" uniqKey="Gauthier S">S Gauthier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Rijk, Mc" uniqKey="De Rijk M">MC De Rijk</name></author><author><name sortKey="Tzourio, C" uniqKey="Tzourio C">C Tzourio</name></author><author><name sortKey="Breteler, Mm" uniqKey="Breteler M">MM Breteler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Calabrese, Vp" uniqKey="Calabrese V">VP Calabrese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Przedborski, S" 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uniqKey="Bayarsaikhan D" first="Delger" last="Bayarsaikhan">Delger Bayarsaikhan</name><name sortKey="Byun, Kyunghee" sort="Byun, Kyunghee" uniqKey="Byun K" first="Kyunghee" last="Byun">Kyunghee Byun</name><name sortKey="Byun, Kyunghee" sort="Byun, Kyunghee" uniqKey="Byun K" first="Kyunghee" last="Byun">Kyunghee Byun</name><name sortKey="Jo, Seung Mook" sort="Jo, Seung Mook" uniqKey="Jo S" first="Seung-Mook" last="Jo">Seung-Mook Jo</name><name sortKey="Lee, Bonghee" sort="Lee, Bonghee" uniqKey="Lee B" first="Bonghee" last="Lee">Bonghee Lee</name><name sortKey="Lee, Bonghee" sort="Lee, Bonghee" uniqKey="Lee B" first="Bonghee" last="Lee">Bonghee Lee</name><name sortKey="Lee, Jaesuk" sort="Lee, Jaesuk" uniqKey="Lee J" first="Jaesuk" last="Lee">Jaesuk Lee</name><name sortKey="Moon, Jeongsik" sort="Moon, Jeongsik" uniqKey="Moon J" first="Jeongsik" last="Moon">Jeongsik Moon</name><name sortKey="Oh, Seyeon" sort="Oh, Seyeon" uniqKey="Oh S" first="Seyeon" last="Oh">Seyeon Oh</name><name sortKey="Park, Hye Jeong" sort="Park, Hye Jeong" uniqKey="Park H" first="Hye-Jeong" last="Park">Hye-Jeong Park</name><name sortKey="Roshini, Arivazhagan" sort="Roshini, Arivazhagan" uniqKey="Roshini A" first="Arivazhagan" last="Roshini">Arivazhagan Roshini</name><name sortKey="Son, Myeongjoo" sort="Son, Myeongjoo" uniqKey="Son M" first="Myeongjoo" last="Son">Myeongjoo Son</name><name sortKey="Son, Myeongjoo" sort="Son, Myeongjoo" uniqKey="Son M" first="Myeongjoo" last="Son">Myeongjoo Son</name></country><country name="Mongolie"><noRegion><name sortKey="Bayarsaikhan, Enkhjargal" sort="Bayarsaikhan, Enkhjargal" uniqKey="Bayarsaikhan E" first="Enkhjargal" last="Bayarsaikhan">Enkhjargal Bayarsaikhan</name></noRegion></country><country name="Canada"><noRegion><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U" last="Kim">Seung U. Kim</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Song, Byoung Joon" sort="Song, Byoung Joon" uniqKey="Song B" first="Byoung-Joon" last="Song">Byoung-Joon Song</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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