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J Pharmacol Sci. 2018 Jun;137(2):146-153. doi: 10.1016/j.jphs.2018.05.004. Epub 2018 May 29.

Neuregulin 1 regulates amyloid precursor protein cell surface expression and non-amyloidogenic processing.

Author information

1
Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, 34824, Republic of Korea.
2
Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongro-gu, Seoul, Republic of Korea.
3
Department of Emergency Medical Technology, Daejeon University, Daejeon, 34520, South Korea.
4
Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, 34824, Republic of Korea. Electronic address: tkbaik@eulji.ac.kr.
5
Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, 34824, Republic of Korea. Electronic address: rswoo@eulji.ac.kr.

Abstract

The amyloid precursor protein (APP) is a key molecule in Alzheimer's disease. The prevailing view is that APP is initially transported to the plasma membrane as a full-length protein. Its localization at the cell surface can trigger downstream signaling and APP cleavage. Our previous work has shown that Neuregulin 1 (NRG1) has neuroprotective effects in an Alzheimer's disease model. In the present study, we examine whether NRG1 signaling is involved in APP expression and non-amyloidogenic processing in neuronal cells. Here we show that NRG1 increased the cell surface expression of APP without changing the total amount of APP mRNA or protein expression in SH-SY5Y cells and in rat primary cortical neurons. In addition, NRG1 significantly increased the levels of the secreted form of APP, sAPPα, in the conditioned media but did not change the expression of ADAM10 on the cell surface or in the cell lysates. Furthermore, we found that the protein level of NRG1 was reduced in the hippocampus of Alzheimer's disease (AD) patients. Our results demonstrate that NRG1 increased APP expression on the cell surface and sAPPα secretion into the media of neuronal cell cultures. Taken together, these results suggest a role for NRG1 in non-amyloidogenic processing.

KEYWORDS:

ADAM10; Amyloid-precursor protein; Neuregulin 1; Non-amyloidogenic processing; Secreted APPα

PMID:
29914798
DOI:
10.1016/j.jphs.2018.05.004
[Indexed for MEDLINE]
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