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SOCS3 induces neurite differentiation and promotes neuronal cell survival
Kanchan Kumar Mishra1, Sakshi Gupta1, Kakoli Banerjee1
1Eukaryotic Gene Expression Lab National Institute of Immunology, New Delhi, India.
Abstract:
Cytokines and growth factors play an important role in neuronal survival as well as cell death. The family of suppressors of cytokine signalling (SOCS) proteins, which includes SOCS1-7 and cytokine-induced suppressor (CIS), has been shown to act as negative regulators of cytokine-induced signalling. In this report, we highlight the role of SOCS3 in regulating neuronal differentiation and survival. We observed increased SOCS3 expression upon differentiation of PC12 cells as well as neural stem cells. SOCS3 overexpression upregulated differentiation of both neural stem cells and PC12 cells even in the absence of NGF, as evidenced by enhanced neurite outgrowth and upregulation of GAP43, marker associated with neurite outgrowth. siRNA-mediated silencing of SOCS3 confirmed the potential role of SOCS3 in neuritogenesis. We observed that, SOCS3-induced neurite differentiation was mediated via the PI3 kinase pathway. Another interesting observation was that SOCS3 overexpression promoted neuronal cell survival under H2 O2 -mediated stress indicating its fundamental role in cell survival. In conclusion, our results indicate that SOCS3 promotes differentiation and survival of neural cells and could be potentially useful in future therapy for treatment of neurodegenerative disorders. © 2016 IUBMB Life, 68(6):468-476, 2016.
Insights
Suppressors of cytokine signaling 3 (SOCS3) protein promotes neural cell differentiation and survival. This protein may be a potential therapeutic target for neurodegenerative disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Cytokines and growth factors are crucial for neuronal survival and death.
- Suppressors of cytokine signaling (SOCS) proteins, including SOCS1-7 and CIS, negatively regulate cytokine signaling.
- SOCS3's specific role in neuronal regulation requires further elucidation.
Purpose of the Study:
- To investigate the role of SOCS3 in neuronal differentiation and survival.
- To explore the underlying molecular mechanisms of SOCS3-mediated neurogenesis.
- To assess the therapeutic potential of SOCS3 in neurodegenerative conditions.
Main Methods:
- Examined SOCS3 expression in differentiating PC12 cells and neural stem cells.
- Utilized SOCS3 overexpression and siRNA-mediated silencing to study its effects.
- Investigated the involvement of the PI3 kinase pathway in SOCS3-induced differentiation.
- Assessed neuronal survival under oxidative stress (H2O2).
Main Results:
- SOCS3 expression increased during neural differentiation.
- SOCS3 overexpression enhanced neurite outgrowth and GAP43 expression, promoting differentiation.
- SOCS3 silencing impaired neuritogenesis.
- SOCS3-induced differentiation involved the PI3 kinase pathway.
- SOCS3 overexpression protected neurons against H2O2-induced oxidative stress.
Conclusions:
- SOCS3 plays a significant role in promoting neural cell differentiation and survival.
- The PI3 kinase pathway mediates SOCS3's effects on neurite differentiation.
- SOCS3 demonstrates potential as a therapeutic agent for neurodegenerative diseases.
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