A combinational treatment of carotenoids decreases Aβ secretion in human neurons via β-secretase inhibition

Misato Sho, Naoki Ichiyanagi, Kent Imaizumi, Mitsuru Ishikawa, Satoru Morimoto, Hirotaka Watanabe, Hideyuki Okano

研究成果: Article

抄録

Alzheimer's disease (AD) is the most common cause of dementia and is characterized neuropathologically by the presence of amyloid plaques and neurofibrillary tangles. Amyloid-β (Aβ) peptides, major components of amyloid plaques and crucial pathogenic molecules in terms of the amyloid hypothesis, are derived from successive proteolytic processing of amyloid-β precursor protein (APP). In this study, we established a human neuronal culture system using induced pluripotent stem cells (iPSCs) to evaluate the possible effects of natural compounds on the amyloid phenotype. Unexpectedly, we found that combinational treatment of carotenoids, but not docosahexaenoic acid, significantly decreased Aβ secretion from iPSC-derived human cortical neurons. Importantly, the effects of the carotenoids resulted from specific inhibition of BACE1 activity and not from expression changes in APP or BACE1. Therefore, these results indicate a novel beneficial function of carotenoids in the anti-amyloidogenic processing of APP. Collectively, this study will shed light on neuronal protection by a novel mechanism during the pathogenesis of AD.

元の言語English
ジャーナルNeuroscience Research
DOI
出版物ステータスAccepted/In press - 2019 1 1

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Amyloid Precursor Protein Secretases
Amyloid beta-Protein Precursor
Carotenoids
Amyloid
Induced Pluripotent Stem Cells
Amyloid Plaques
Neurons
Alzheimer Disease
Neurofibrillary Tangles
Docosahexaenoic Acids
Dementia
Phenotype
Peptides
Inhibition (Psychology)

ASJC Scopus subject areas

  • Neuroscience(all)

これを引用

A combinational treatment of carotenoids decreases Aβ secretion in human neurons via β-secretase inhibition. / Sho, Misato; Ichiyanagi, Naoki; Imaizumi, Kent; Ishikawa, Mitsuru; Morimoto, Satoru; Watanabe, Hirotaka; Okano, Hideyuki.

:: Neuroscience Research, 01.01.2019.

研究成果: Article

Sho, Misato ; Ichiyanagi, Naoki ; Imaizumi, Kent ; Ishikawa, Mitsuru ; Morimoto, Satoru ; Watanabe, Hirotaka ; Okano, Hideyuki. / A combinational treatment of carotenoids decreases Aβ secretion in human neurons via β-secretase inhibition. :: Neuroscience Research. 2019.
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AU - Sho, Misato

AU - Ichiyanagi, Naoki

AU - Imaizumi, Kent

AU - Ishikawa, Mitsuru

AU - Morimoto, Satoru

AU - Watanabe, Hirotaka

AU - Okano, Hideyuki

PY - 2019/1/1

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N2 - Alzheimer's disease (AD) is the most common cause of dementia and is characterized neuropathologically by the presence of amyloid plaques and neurofibrillary tangles. Amyloid-β (Aβ) peptides, major components of amyloid plaques and crucial pathogenic molecules in terms of the amyloid hypothesis, are derived from successive proteolytic processing of amyloid-β precursor protein (APP). In this study, we established a human neuronal culture system using induced pluripotent stem cells (iPSCs) to evaluate the possible effects of natural compounds on the amyloid phenotype. Unexpectedly, we found that combinational treatment of carotenoids, but not docosahexaenoic acid, significantly decreased Aβ secretion from iPSC-derived human cortical neurons. Importantly, the effects of the carotenoids resulted from specific inhibition of BACE1 activity and not from expression changes in APP or BACE1. Therefore, these results indicate a novel beneficial function of carotenoids in the anti-amyloidogenic processing of APP. Collectively, this study will shed light on neuronal protection by a novel mechanism during the pathogenesis of AD.

AB - Alzheimer's disease (AD) is the most common cause of dementia and is characterized neuropathologically by the presence of amyloid plaques and neurofibrillary tangles. Amyloid-β (Aβ) peptides, major components of amyloid plaques and crucial pathogenic molecules in terms of the amyloid hypothesis, are derived from successive proteolytic processing of amyloid-β precursor protein (APP). In this study, we established a human neuronal culture system using induced pluripotent stem cells (iPSCs) to evaluate the possible effects of natural compounds on the amyloid phenotype. Unexpectedly, we found that combinational treatment of carotenoids, but not docosahexaenoic acid, significantly decreased Aβ secretion from iPSC-derived human cortical neurons. Importantly, the effects of the carotenoids resulted from specific inhibition of BACE1 activity and not from expression changes in APP or BACE1. Therefore, these results indicate a novel beneficial function of carotenoids in the anti-amyloidogenic processing of APP. Collectively, this study will shed light on neuronal protection by a novel mechanism during the pathogenesis of AD.

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KW - Cortical neurons

KW - Induced pluripotent stem cells

KW - β-secretase

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