Pan-HDAC inhibitors promote tau aggregation by increasing the level of acetylated TAU

Hyeanjeong Jeong; Seulgi Shin; Jun Seok Lee; Soo Hyun Lee; Ja Hyun Baik; Sungsu Lim; Yun Kyung Kim

doi:10.3390/ijms20174283

Pan-HDAC inhibitors promote tau aggregation by increasing the level of acetylated TAU

Hyeanjeong Jeong, Seulgi Shin, Jun Seok Lee, Soo Hyun Lee, Ja Hyun Baik, Sungsu Lim, Yun Kyung Kim

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

9 Citations (Scopus)

Abstract

Epigenetic remodeling via histone acetylation has become a popular therapeutic strategy to treat Alzheimer’s disease (AD). In particular, histone deacetylase (HDAC) inhibitors including M344 and SAHA have been elucidated to be new drug candidates for AD, improving cognitive abilities impaired in AD mouse models. Although emerged as a promising target for AD, most of the HDAC inhibitors are poorly selective and could cause unwanted side effects. Here we show that tau is one of the cytosolic substrates of HDAC and the treatment of HDAC inhibitors such as Scriptaid, M344, BML281, and SAHA could increase the level of acetylated tau, resulting in the activation of tau pathology.

Original language	English
Article number	4283
Journal	International journal of molecular sciences
Volume	20
Issue number	17
DOIs	https://doi.org/10.3390/ijms20174283
Publication status	Published - 2019 Sept 1

Keywords

Alzheimer’s disease
Histone deacetylase inhibitor
Tau acetylation
Tau aggregation

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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title = "Pan-HDAC inhibitors promote tau aggregation by increasing the level of acetylated TAU",

abstract = "Epigenetic remodeling via histone acetylation has become a popular therapeutic strategy to treat Alzheimer{\textquoteright}s disease (AD). In particular, histone deacetylase (HDAC) inhibitors including M344 and SAHA have been elucidated to be new drug candidates for AD, improving cognitive abilities impaired in AD mouse models. Although emerged as a promising target for AD, most of the HDAC inhibitors are poorly selective and could cause unwanted side effects. Here we show that tau is one of the cytosolic substrates of HDAC and the treatment of HDAC inhibitors such as Scriptaid, M344, BML281, and SAHA could increase the level of acetylated tau, resulting in the activation of tau pathology.",

keywords = "Alzheimer{\textquoteright}s disease, Histone deacetylase inhibitor, Tau acetylation, Tau aggregation",

author = "Hyeanjeong Jeong and Seulgi Shin and Lee, {Jun Seok} and Lee, {Soo Hyun} and Baik, {Ja Hyun} and Sungsu Lim and Kim, {Yun Kyung}",

note = "Funding Information: This work was supported by grants from the following funding agencies: the National Research Council of Science & Technology (NST) granted by the Ministry of Science, ICT & Future Planning (MSIP) (No. CRC-15-04-KIST); the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the MSIP (2016M3C7A1913845); the Basic Science Research program through the NRF funded by the Ministry of Education (2017R1A6A3A04012384); the Korea Institute Science and Technology (KIST) Institutional Program, Young Fellow Award (2V06480); and the KBRI basic research program through Korea Brain Research Institute funded by the Ministry of Science & ICT (19-BR-03-02). Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/ijms20174283",

language = "English",

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AU - Jeong, Hyeanjeong

AU - Shin, Seulgi

AU - Lee, Jun Seok

AU - Lee, Soo Hyun

AU - Baik, Ja Hyun

AU - Lim, Sungsu

AU - Kim, Yun Kyung

N1 - Funding Information: This work was supported by grants from the following funding agencies: the National Research Council of Science & Technology (NST) granted by the Ministry of Science, ICT & Future Planning (MSIP) (No. CRC-15-04-KIST); the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the MSIP (2016M3C7A1913845); the Basic Science Research program through the NRF funded by the Ministry of Education (2017R1A6A3A04012384); the Korea Institute Science and Technology (KIST) Institutional Program, Young Fellow Award (2V06480); and the KBRI basic research program through Korea Brain Research Institute funded by the Ministry of Science & ICT (19-BR-03-02). Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Epigenetic remodeling via histone acetylation has become a popular therapeutic strategy to treat Alzheimer’s disease (AD). In particular, histone deacetylase (HDAC) inhibitors including M344 and SAHA have been elucidated to be new drug candidates for AD, improving cognitive abilities impaired in AD mouse models. Although emerged as a promising target for AD, most of the HDAC inhibitors are poorly selective and could cause unwanted side effects. Here we show that tau is one of the cytosolic substrates of HDAC and the treatment of HDAC inhibitors such as Scriptaid, M344, BML281, and SAHA could increase the level of acetylated tau, resulting in the activation of tau pathology.

AB - Epigenetic remodeling via histone acetylation has become a popular therapeutic strategy to treat Alzheimer’s disease (AD). In particular, histone deacetylase (HDAC) inhibitors including M344 and SAHA have been elucidated to be new drug candidates for AD, improving cognitive abilities impaired in AD mouse models. Although emerged as a promising target for AD, most of the HDAC inhibitors are poorly selective and could cause unwanted side effects. Here we show that tau is one of the cytosolic substrates of HDAC and the treatment of HDAC inhibitors such as Scriptaid, M344, BML281, and SAHA could increase the level of acetylated tau, resulting in the activation of tau pathology.

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Pan-HDAC inhibitors promote tau aggregation by increasing the level of acetylated TAU

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Keywords

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