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Coniferaldehyde attenuates Alzheimer's pathology via activation of Nrf2 and its targets
Background: Alzheimer's disease (AD) currently lacks a cure. Because substantial neuronal damage usually occurs before AD is advanced enough for diagnosis, the best hope for disease-modifying AD therapies likely relies on early intervention or even prevention, and targeting multiple pathways im...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929631/ https://www.ncbi.nlm.nih.gov/pubmed/31903114 http://dx.doi.org/10.7150/thno.36722 |
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author | Dong, Yaqiong Stewart, Tessandra Bai, Lidan Li, Xue Xu, Ting Iliff, Jeffrey Shi, Min Zheng, Danfeng Yuan, Lan Wei, Taotao Yang, Xiaoda Zhang, Jing |
author_facet | Dong, Yaqiong Stewart, Tessandra Bai, Lidan Li, Xue Xu, Ting Iliff, Jeffrey Shi, Min Zheng, Danfeng Yuan, Lan Wei, Taotao Yang, Xiaoda Zhang, Jing |
author_sort | Dong, Yaqiong |
collection | PubMed |
description | Background: Alzheimer's disease (AD) currently lacks a cure. Because substantial neuronal damage usually occurs before AD is advanced enough for diagnosis, the best hope for disease-modifying AD therapies likely relies on early intervention or even prevention, and targeting multiple pathways implicated in early AD pathogenesis rather than focusing exclusively on excessive production of β-amyloid (Aβ) species. Methods: Coniferaldehyde (CFA), a food flavoring and agonist of NF-E2-related factor 2 (Nrf2), was selected by multimodal in vitro screening, followed by investigation of several downstream effects potentially involved. Furthermore, in the APP/PS1 AD mouse model, the therapeutic effects of CFA (0.2 mmol kg(-1)d(-1)) were tested beginning at 3 months of age. Behavioral phenotypes related to learning and memory capacity, brain pathology and biochemistry, including Aβ transport, were assessed at different time intervals. Results: CFA promoted neuron viability and showed potent neuroprotective effects, especially on mitochondrial structure and functions. In addition, CFA greatly enhanced the brain clearance of Aβ in both free and extracellular vesicle (EV)-contained Aβ forms. In the APP/PS1 mouse model, CFA effectively abolished brain Aβ deposits and reduced the level of toxic soluble Aβ peptides, thus eliminating AD-like pathological changes in the hippocampus and cerebral cortex and preserving learning and memory capacity of the mice. Conclusion: The experimental evidence overall indicated that Nrf2 activation may contribute to the potent anti-AD effects of CFA. With an excellent safety profile, further clinical investigation of coniferaldehyde might bring hope for AD prevention/therapy. |
format | Online Article Text |
id | pubmed-6929631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-69296312020-01-04 Coniferaldehyde attenuates Alzheimer's pathology via activation of Nrf2 and its targets Dong, Yaqiong Stewart, Tessandra Bai, Lidan Li, Xue Xu, Ting Iliff, Jeffrey Shi, Min Zheng, Danfeng Yuan, Lan Wei, Taotao Yang, Xiaoda Zhang, Jing Theranostics Research Paper Background: Alzheimer's disease (AD) currently lacks a cure. Because substantial neuronal damage usually occurs before AD is advanced enough for diagnosis, the best hope for disease-modifying AD therapies likely relies on early intervention or even prevention, and targeting multiple pathways implicated in early AD pathogenesis rather than focusing exclusively on excessive production of β-amyloid (Aβ) species. Methods: Coniferaldehyde (CFA), a food flavoring and agonist of NF-E2-related factor 2 (Nrf2), was selected by multimodal in vitro screening, followed by investigation of several downstream effects potentially involved. Furthermore, in the APP/PS1 AD mouse model, the therapeutic effects of CFA (0.2 mmol kg(-1)d(-1)) were tested beginning at 3 months of age. Behavioral phenotypes related to learning and memory capacity, brain pathology and biochemistry, including Aβ transport, were assessed at different time intervals. Results: CFA promoted neuron viability and showed potent neuroprotective effects, especially on mitochondrial structure and functions. In addition, CFA greatly enhanced the brain clearance of Aβ in both free and extracellular vesicle (EV)-contained Aβ forms. In the APP/PS1 mouse model, CFA effectively abolished brain Aβ deposits and reduced the level of toxic soluble Aβ peptides, thus eliminating AD-like pathological changes in the hippocampus and cerebral cortex and preserving learning and memory capacity of the mice. Conclusion: The experimental evidence overall indicated that Nrf2 activation may contribute to the potent anti-AD effects of CFA. With an excellent safety profile, further clinical investigation of coniferaldehyde might bring hope for AD prevention/therapy. Ivyspring International Publisher 2020-01-01 /pmc/articles/PMC6929631/ /pubmed/31903114 http://dx.doi.org/10.7150/thno.36722 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Dong, Yaqiong Stewart, Tessandra Bai, Lidan Li, Xue Xu, Ting Iliff, Jeffrey Shi, Min Zheng, Danfeng Yuan, Lan Wei, Taotao Yang, Xiaoda Zhang, Jing Coniferaldehyde attenuates Alzheimer's pathology via activation of Nrf2 and its targets |
title | Coniferaldehyde attenuates Alzheimer's pathology via activation of Nrf2 and its targets |
title_full | Coniferaldehyde attenuates Alzheimer's pathology via activation of Nrf2 and its targets |
title_fullStr | Coniferaldehyde attenuates Alzheimer's pathology via activation of Nrf2 and its targets |
title_full_unstemmed | Coniferaldehyde attenuates Alzheimer's pathology via activation of Nrf2 and its targets |
title_short | Coniferaldehyde attenuates Alzheimer's pathology via activation of Nrf2 and its targets |
title_sort | coniferaldehyde attenuates alzheimer's pathology via activation of nrf2 and its targets |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929631/ https://www.ncbi.nlm.nih.gov/pubmed/31903114 http://dx.doi.org/10.7150/thno.36722 |
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