BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia
Zhengrong Zhang1, Jing Huang1, Yong Shen2,3,4
1National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical UniversityBeijing, China.
Frontiers in Molecular Neuroscience
|October 11, 2017
Summary
Neuregulin-1 (Nrg1) cleavage by beta-secretase 1 (BACE1) impacts schizophrenia. Understanding this Nrg1-BACE1 interaction may offer diagnostic biomarkers and therapeutic targets for schizophrenia.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Schizophrenia affects 1% of the population, with Neuregulin-1 (Nrg1) identified as a candidate gene.
- Nrg1 isoforms contain an epidermal growth factor (EGF)-like domain crucial for myelin sheath formation and synaptic plasticity.
- Nrg1 cleavage by beta-secretase 1 (BACE1) produces a fragment that binds ErbB4, activating Nrg1/ErbB4 signaling.
Purpose of the Study:
- To review the role of BACE1-cleaved Nrg1-ntf and Nrg1/ErbB4 signaling in schizophrenia neuropathogenesis.
- To explore Nrg1 structure, BACE1 cleavage patterns, and their association with schizophrenia.
- To examine human and animal studies investigating Nrg1 and BACE1 in schizophrenia.
Main Methods:
- Review of existing literature on Nrg1 structure and BACE1 cleavage.
- Analysis of human studies examining BACE1-dependent Nrg1 cleavage in schizophrenia.
- Evaluation of animal studies involving Nrg1 and BACE1 mutations and behavioral observations.
Main Results:
- Nrg1 expression changes in schizophrenia are debated, but BACE1 cleavage is critical.
- Human studies link BACE1-dependent Nrg1 cleavage to schizophrenia.
- Animal models with Nrg1/BACE1 mutations show behavioral alterations relevant to schizophrenia.
Conclusions:
- BACE1 cleavage of Nrg1 is a significant factor in schizophrenia.
- Nrg1/ErbB4 signaling pathways are implicated in schizophrenia.
- BACE1 cleavage of Nrg1 presents potential as a diagnostic biomarker and therapeutic target for schizophrenia.
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