Nec-1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice

Seung Hoon Yang; Dongkeun Kenneth Lee; Jisu Shin; Sejin Lee; Seungyeop Baek; Jiyoon Kim; Hoyong Jung; Jung Mi Hah; Young Soo Kim

doi:10.15252/emmm.201606566

Nec-1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice

Seung Hoon Yang, Dongkeun Kenneth Lee, Jisu Shin, Sejin Lee, Seungyeop Baek, Jiyoon Kim, Hoyong Jung, Jung Mi Hah, Young Soo Kim

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

68 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is as an important target of treatment as other classical hallmarks of AD, such as aggregation of amyloid-β (Aβ) and hyperphosphorylation of tau. Here, we found that an anti-necroptotic molecule necrostatin-1 (Nec-1) directly targets Aβ and tau proteins, alleviates brain cell death and ameliorates cognitive impairment in AD models. In the cortex and hippocampus of APP/PS1 double-transgenic mice, Nec-1 treatment reduced the levels of Aβ oligomers, plaques and hyperphosphorylated tau without affecting production of Aβ, while it altered the levels of apoptotic marker proteins. Our results showing multiple beneficial modes of action of Nec-1 against AD provide evidence that Nec-1 may serve an important role in the development of preventive approach for AD.

Original language	English
Pages (from-to)	61-77
Number of pages	17
Journal	EMBO Molecular Medicine
Volume	9
Issue number	1
DOIs	https://doi.org/10.15252/emmm.201606566
Publication status	Published - 2017 Jan 1

Bibliographical note

Funding Information:
This research was supported by National Research Council of Science & Technology (NST, CRC-15-04-KIST), Basic Science Research Program through the National Research Foundation of Korea (NRF, 2015R1A6A3A04058568 and 2014R1A1A3051648) funded by the Ministry of Education, Science and Technology, and Korea Institute of Science and Technology (KIST Young Fellowship, 2V05030). The authors thank Mr. Yakdol Cho (Korea Institute of Science and Technology) for animal maintenance and preparation; Dr. Yun Kyung Kim (Korea Institute of Science and Technology) and Dr. Sungsu Lim (Korea Institute of Science and Technology) for preparation of tau aggregation; Mr. Juhyeong Jo (GE Healthcare Korea/Japan) for Biacore analyses; and Ms. Sarah Hesse (University of Glasgow) for editing advices. The authors appreciate Dr. Hye Yun Kim for scientific advices.

Publisher Copyright:
© 2016 The Authors. Published under the terms of the CC BY 4.0 license

All Science Journal Classification (ASJC) codes

Molecular Medicine

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title = "Nec-1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice",

abstract = "Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is as an important target of treatment as other classical hallmarks of AD, such as aggregation of amyloid-β (Aβ) and hyperphosphorylation of tau. Here, we found that an anti-necroptotic molecule necrostatin-1 (Nec-1) directly targets Aβ and tau proteins, alleviates brain cell death and ameliorates cognitive impairment in AD models. In the cortex and hippocampus of APP/PS1 double-transgenic mice, Nec-1 treatment reduced the levels of Aβ oligomers, plaques and hyperphosphorylated tau without affecting production of Aβ, while it altered the levels of apoptotic marker proteins. Our results showing multiple beneficial modes of action of Nec-1 against AD provide evidence that Nec-1 may serve an important role in the development of preventive approach for AD.",

author = "Yang, {Seung Hoon} and Lee, {Dongkeun Kenneth} and Jisu Shin and Sejin Lee and Seungyeop Baek and Jiyoon Kim and Hoyong Jung and Hah, {Jung Mi} and Kim, {Young Soo}",

note = "Funding Information: This research was supported by National Research Council of Science & Technology (NST, CRC-15-04-KIST), Basic Science Research Program through the National Research Foundation of Korea (NRF, 2015R1A6A3A04058568 and 2014R1A1A3051648) funded by the Ministry of Education, Science and Technology, and Korea Institute of Science and Technology (KIST Young Fellowship, 2V05030). The authors thank Mr. Yakdol Cho (Korea Institute of Science and Technology) for animal maintenance and preparation; Dr. Yun Kyung Kim (Korea Institute of Science and Technology) and Dr. Sungsu Lim (Korea Institute of Science and Technology) for preparation of tau aggregation; Mr. Juhyeong Jo (GE Healthcare Korea/Japan) for Biacore analyses; and Ms. Sarah Hesse (University of Glasgow) for editing advices. The authors appreciate Dr. Hye Yun Kim for scientific advices. Publisher Copyright: {\textcopyright} 2016 The Authors. Published under the terms of the CC BY 4.0 license",

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doi = "10.15252/emmm.201606566",

language = "English",

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Nec-1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice. / Yang, Seung Hoon; Lee, Dongkeun Kenneth; Shin, Jisu; Lee, Sejin; Baek, Seungyeop; Kim, Jiyoon; Jung, Hoyong; Hah, Jung Mi; Kim, Young Soo.

In: EMBO Molecular Medicine, Vol. 9, No. 1, 01.01.2017, p. 61-77.

Research output: Contribution to journal › Article › peer-review

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AU - Kim, Jiyoon

AU - Jung, Hoyong

AU - Hah, Jung Mi

AU - Kim, Young Soo

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N2 - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is as an important target of treatment as other classical hallmarks of AD, such as aggregation of amyloid-β (Aβ) and hyperphosphorylation of tau. Here, we found that an anti-necroptotic molecule necrostatin-1 (Nec-1) directly targets Aβ and tau proteins, alleviates brain cell death and ameliorates cognitive impairment in AD models. In the cortex and hippocampus of APP/PS1 double-transgenic mice, Nec-1 treatment reduced the levels of Aβ oligomers, plaques and hyperphosphorylated tau without affecting production of Aβ, while it altered the levels of apoptotic marker proteins. Our results showing multiple beneficial modes of action of Nec-1 against AD provide evidence that Nec-1 may serve an important role in the development of preventive approach for AD.

AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is as an important target of treatment as other classical hallmarks of AD, such as aggregation of amyloid-β (Aβ) and hyperphosphorylation of tau. Here, we found that an anti-necroptotic molecule necrostatin-1 (Nec-1) directly targets Aβ and tau proteins, alleviates brain cell death and ameliorates cognitive impairment in AD models. In the cortex and hippocampus of APP/PS1 double-transgenic mice, Nec-1 treatment reduced the levels of Aβ oligomers, plaques and hyperphosphorylated tau without affecting production of Aβ, while it altered the levels of apoptotic marker proteins. Our results showing multiple beneficial modes of action of Nec-1 against AD provide evidence that Nec-1 may serve an important role in the development of preventive approach for AD.

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Nec-1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice

Abstract

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