BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia
Schizophrenia is a chronic psychiatric disorder with a lifetime prevalence of about 1% in the general population. Recent studies have shown that Neuregulin-1 (Nrg1) is a candidate gene for schizophrenia. At least 15 alternative splicing of NRG1 isoforms all contain an extracellular epidermal growth...
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doaj-1d991296405d49aa80fa17dde912e8652020-11-24T21:09:06ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-09-011010.3389/fnmol.2017.00302284785BACE1-Dependent Neuregulin-1 Signaling: An Implication for SchizophreniaZhengrong Zhang0Jing Huang1Yong Shen2Yong Shen3Yong Shen4Rena Li5Rena Li6Rena Li7Rena Li8National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing, ChinaNational Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing, ChinaNeurodegenerative Disorder Research Center, School of Life Sciences, University of Science and Technology of ChinaHefei, ChinaCenter for Therapeutic Strategies for Brain Disorders, Roskamp Institute, SarasotaFL, United StatesCenter for Hormone Advanced Science and Education, Roskamp Institute, SarasotaFL, United StatesNational Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing, ChinaCenter for Therapeutic Strategies for Brain Disorders, Roskamp Institute, SarasotaFL, United StatesCenter for Hormone Advanced Science and Education, Roskamp Institute, SarasotaFL, United StatesBeijing Institute for Brain Disorders, Capital Medical UniversityBeijing, ChinaSchizophrenia is a chronic psychiatric disorder with a lifetime prevalence of about 1% in the general population. Recent studies have shown that Neuregulin-1 (Nrg1) is a candidate gene for schizophrenia. At least 15 alternative splicing of NRG1 isoforms all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1 biological activity including the formation of myelin sheaths and the regulation of synaptic plasticity. It is known that Nrg1 can be cleaved by β-secretase (BACE1) and the resulting N-terminal fragment (Nrg1-ntf) binds to receptor tyrosine kinase ErbB4, which activates Nrg1/ErbB4 signaling. While changes in Nrg1 expression levels in schizophrenia still remain controversial, understanding the BACE1-cleaved Nrg1-ntf and Nrg1/ErbB4 signaling in schizophrenia neuropathogenesis is essential and important. In this review paper, we included three major parts: (1) Nrg1 structure and cleavage pattern by BACE1; (2) BACE1-dependent Nrg1 cleavage associated with schizophrenia in human studies; and (3) Animal studies of Nrg1 and BACE1 mutations with behavioral observations. Our review will provide a better understanding of Nrg1 in schizophrenia and a potential strategy for using BACE1 cleavage of Nrg1 as a unique biomarker for diagnosis, as well as a new therapeutic target, of schizophrenia.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00302/fullschizophreniaβ-secretase (BACE1)neuregulin-1 (NRG1)erb-b2 receptor tyrosine kinase 4 (ErbB4)signaling pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhengrong Zhang Jing Huang Yong Shen Yong Shen Yong Shen Rena Li Rena Li Rena Li Rena Li |
spellingShingle |
Zhengrong Zhang Jing Huang Yong Shen Yong Shen Yong Shen Rena Li Rena Li Rena Li Rena Li BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia Frontiers in Molecular Neuroscience schizophrenia β-secretase (BACE1) neuregulin-1 (NRG1) erb-b2 receptor tyrosine kinase 4 (ErbB4) signaling pathway |
author_facet |
Zhengrong Zhang Jing Huang Yong Shen Yong Shen Yong Shen Rena Li Rena Li Rena Li Rena Li |
author_sort |
Zhengrong Zhang |
title |
BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia |
title_short |
BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia |
title_full |
BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia |
title_fullStr |
BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia |
title_full_unstemmed |
BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia |
title_sort |
bace1-dependent neuregulin-1 signaling: an implication for schizophrenia |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2017-09-01 |
description |
Schizophrenia is a chronic psychiatric disorder with a lifetime prevalence of about 1% in the general population. Recent studies have shown that Neuregulin-1 (Nrg1) is a candidate gene for schizophrenia. At least 15 alternative splicing of NRG1 isoforms all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1 biological activity including the formation of myelin sheaths and the regulation of synaptic plasticity. It is known that Nrg1 can be cleaved by β-secretase (BACE1) and the resulting N-terminal fragment (Nrg1-ntf) binds to receptor tyrosine kinase ErbB4, which activates Nrg1/ErbB4 signaling. While changes in Nrg1 expression levels in schizophrenia still remain controversial, understanding the BACE1-cleaved Nrg1-ntf and Nrg1/ErbB4 signaling in schizophrenia neuropathogenesis is essential and important. In this review paper, we included three major parts: (1) Nrg1 structure and cleavage pattern by BACE1; (2) BACE1-dependent Nrg1 cleavage associated with schizophrenia in human studies; and (3) Animal studies of Nrg1 and BACE1 mutations with behavioral observations. Our review will provide a better understanding of Nrg1 in schizophrenia and a potential strategy for using BACE1 cleavage of Nrg1 as a unique biomarker for diagnosis, as well as a new therapeutic target, of schizophrenia. |
topic |
schizophrenia β-secretase (BACE1) neuregulin-1 (NRG1) erb-b2 receptor tyrosine kinase 4 (ErbB4) signaling pathway |
url |
http://journal.frontiersin.org/article/10.3389/fnmol.2017.00302/full |
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