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Coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 targeting inflammation and oxidative stress to protect BE(2)-M17 cells against α-synuclein toxicity
Parkinson’s disease (PD) is featured mainly by the loss of dopaminergic neurons and the presence of α-synuclein-containing aggregates in the substantia nigra of brain. The α-synuclein fibrils and aggregates lead to increased oxidative stress and neural toxicity in PD. Chronic inflammation mediated b...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497001/ https://www.ncbi.nlm.nih.gov/pubmed/37578928 http://dx.doi.org/10.18632/aging.204954 |
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author | Yang, Pei-Ning Chen, Wan-Ling Lee, Jun-Wei Lin, Chih-Hsin Chen, Yi-Ru Lin, Chung-Yin Lin, Wenwei Yao, Ching-Fa Wu, Yih-Ru Chang, Kuo-Hsuan Chen, Chiung-Mei Lee-Chen, Guey-Jen |
author_facet | Yang, Pei-Ning Chen, Wan-Ling Lee, Jun-Wei Lin, Chih-Hsin Chen, Yi-Ru Lin, Chung-Yin Lin, Wenwei Yao, Ching-Fa Wu, Yih-Ru Chang, Kuo-Hsuan Chen, Chiung-Mei Lee-Chen, Guey-Jen |
author_sort | Yang, Pei-Ning |
collection | PubMed |
description | Parkinson’s disease (PD) is featured mainly by the loss of dopaminergic neurons and the presence of α-synuclein-containing aggregates in the substantia nigra of brain. The α-synuclein fibrils and aggregates lead to increased oxidative stress and neural toxicity in PD. Chronic inflammation mediated by microglia is one of the hallmarks of PD pathophysiology. In this report, we showed that coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 reduced the expression of major histocompatibility complex-II, NLR family pyrin domain containing (NLRP) 3, caspase-1, inducible nitric oxide synthase, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in α-synuclein-activated mouse BV-2 microglia. Release of pro-inflammatory mediators including nitric oxide, IL-1β, IL-6 and TNF-α was also mitigated. In BE(2)-M17 cells expressing A53T α-synuclein aggregates, LM-021 and NC009-1 reduced α-synuclein aggregation, neuroinflammation, oxidative stress and apoptosis, and promoted neurite outgrowth. These protective effects were mediated by downregulating NLRP1, IL-1β and IL-6, and their downstream pathways including nuclear factor (NF)-κB inhibitor alpha (IκBα)/NF-κB P65 subunit (P65), c-Jun N-terminal kinase (JNK)/proto-oncogene c-Jun (JUN), mitogen-activated protein kinase 14 (P38)/signal transducer and activator of transcription (STAT) 1, and Janus kinase 2 (JAK2)/STAT3. The study results indicate LM-021 and NC009-1 as potential new drug candidates for PD. |
format | Online Article Text |
id | pubmed-10497001 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-104970012023-09-13 Coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 targeting inflammation and oxidative stress to protect BE(2)-M17 cells against α-synuclein toxicity Yang, Pei-Ning Chen, Wan-Ling Lee, Jun-Wei Lin, Chih-Hsin Chen, Yi-Ru Lin, Chung-Yin Lin, Wenwei Yao, Ching-Fa Wu, Yih-Ru Chang, Kuo-Hsuan Chen, Chiung-Mei Lee-Chen, Guey-Jen Aging (Albany NY) Research Paper Parkinson’s disease (PD) is featured mainly by the loss of dopaminergic neurons and the presence of α-synuclein-containing aggregates in the substantia nigra of brain. The α-synuclein fibrils and aggregates lead to increased oxidative stress and neural toxicity in PD. Chronic inflammation mediated by microglia is one of the hallmarks of PD pathophysiology. In this report, we showed that coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 reduced the expression of major histocompatibility complex-II, NLR family pyrin domain containing (NLRP) 3, caspase-1, inducible nitric oxide synthase, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in α-synuclein-activated mouse BV-2 microglia. Release of pro-inflammatory mediators including nitric oxide, IL-1β, IL-6 and TNF-α was also mitigated. In BE(2)-M17 cells expressing A53T α-synuclein aggregates, LM-021 and NC009-1 reduced α-synuclein aggregation, neuroinflammation, oxidative stress and apoptosis, and promoted neurite outgrowth. These protective effects were mediated by downregulating NLRP1, IL-1β and IL-6, and their downstream pathways including nuclear factor (NF)-κB inhibitor alpha (IκBα)/NF-κB P65 subunit (P65), c-Jun N-terminal kinase (JNK)/proto-oncogene c-Jun (JUN), mitogen-activated protein kinase 14 (P38)/signal transducer and activator of transcription (STAT) 1, and Janus kinase 2 (JAK2)/STAT3. The study results indicate LM-021 and NC009-1 as potential new drug candidates for PD. Impact Journals 2023-08-11 /pmc/articles/PMC10497001/ /pubmed/37578928 http://dx.doi.org/10.18632/aging.204954 Text en Copyright: © 2023 Yang et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Yang, Pei-Ning Chen, Wan-Ling Lee, Jun-Wei Lin, Chih-Hsin Chen, Yi-Ru Lin, Chung-Yin Lin, Wenwei Yao, Ching-Fa Wu, Yih-Ru Chang, Kuo-Hsuan Chen, Chiung-Mei Lee-Chen, Guey-Jen Coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 targeting inflammation and oxidative stress to protect BE(2)-M17 cells against α-synuclein toxicity |
title | Coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 targeting inflammation and oxidative stress to protect BE(2)-M17 cells against α-synuclein toxicity |
title_full | Coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 targeting inflammation and oxidative stress to protect BE(2)-M17 cells against α-synuclein toxicity |
title_fullStr | Coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 targeting inflammation and oxidative stress to protect BE(2)-M17 cells against α-synuclein toxicity |
title_full_unstemmed | Coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 targeting inflammation and oxidative stress to protect BE(2)-M17 cells against α-synuclein toxicity |
title_short | Coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 targeting inflammation and oxidative stress to protect BE(2)-M17 cells against α-synuclein toxicity |
title_sort | coumarin-chalcone hybrid lm-021 and indole derivative nc009-1 targeting inflammation and oxidative stress to protect be(2)-m17 cells against α-synuclein toxicity |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497001/ https://www.ncbi.nlm.nih.gov/pubmed/37578928 http://dx.doi.org/10.18632/aging.204954 |
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