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Estrogen Regulation of the Neprilysin Gene Through A Hormone-Responsive Element

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Abstract

Our previous data showed that neprilysin (NEP), a zinc metalloendopeptidase, which can degrade amyloid-β peptide (Aβ) whose central nerve system accumulation is the primary cause of Alzheimer’s disease (AD), responds to estrogen in the brain. Recently, it has been shown that the transcription of the neprilysin gene can be up regulated by progesterone, androgens, and glucocorticoids through two androgen response elements within the NEP gene—an androgen response region (ARR) and an androgen response element (ARE). Through a yeast report gene system, we now find that the ARR but not the ARE respond to estrogen. However, androgen could efficiently enhance the expression of the report gene mainly through ARE. Our results indicate that the decrease of NEP, caused by the decline of estrogen or androgen with aging, may be an important factor leading to Aβ accumulation and AD.

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Acknowledgements

We are grateful to Dr. Dan Noonan for the yeast strains and plasmids he kindly presented. We are grateful to Dr. Louis Hersh and Dr. Dan Noonan for the scientific advice during the course of this study. This work was supported by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of China (2004527), Hubei Province Natural Science Foundation of China (2006ABA219), and National Natural Science Foundation of China (30670647).

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Authors and Affiliations

  1. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, China

    Zhi-Min Xiao, Li Sun & Jian Huang

  2. Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China

    Yu-Min Liu & Jun-Jian Zhang

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  1. Zhi-Min Xiao
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  2. Li Sun
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  3. Yu-Min Liu
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  4. Jun-Jian Zhang
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  5. Jian Huang
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Correspondence to Jian Huang.

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Xiao, ZM., Sun, L., Liu, YM. et al. Estrogen Regulation of the Neprilysin Gene Through A Hormone-Responsive Element. J Mol Neurosci 39, 22–26 (2009). https://doi.org/10.1007/s12031-008-9168-1

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  • DOI: https://doi.org/10.1007/s12031-008-9168-1

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