Regulation of the JAK/STAT signaling pathway in spinal cord injury: an updated review

Frontiers in Immunology, 2023 · DOI: 10.3389/fimmu.2023.1276445 · Published: November 8, 2023

Simple Explanation

Cytokines, signaling molecules, play a crucial role in neuroinflammation after spinal cord injury (SCI). Their effects are mediated through the JAK/STAT pathway. Targeting this pathway with small-molecule inhibitors could be a potential treatment strategy for SCI. The JAK/STAT signaling pathway is a fundamental part of the eukaryotic cell cycle, which affects cell growth, survival, development and differentiation. The activation of the JAK and STAT signaling pathway is an important pathway for signal transmission from the cell surface to the nucleus. Cell membrane JAK activation leads to STAT phosphorylation in the cytoplasm and signal transmission from phosphorylated STAT to the nucleus, followed by target gene translocation, which plays an important role in pathophysiological changes after SCIs.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
The JAK/STAT pathway is involved in the proliferation and differentiation of neural stem cells, promoting the regeneration of astrocytes and inducing the differentiation of neurons and oligodendrocytes.
2
Reactive astrocytes, whose role in SCIs is to separate the spinal cord lesion sites from healthy spinal cord tissues, prevent greater inﬂammatory responses, massive cellular degenerative deaths and tissue damage in secondary injuries.
3
The JAK/STAT pathway affects microglia activation, astrocyte proliferation, and the differentiation of endogenous neural stem cells after SCIs, influencing inflammation, scar tissue formation, and nerve regeneration.

Research Summary

This review describes the current understanding of the JAK-STAT signaling in neuroendocrine homeostasis and diseases, together with the rationale for targeting at this pathway for the treatment of SCI. JAK/STAT receptor-mediated activation leads to T cell differentiation in thymic or inﬂammatory loci. Molecules that interfere with these interactions, particularly small molecules targeting at JAKs and STATs, have shown a good efﬁcacy and safety in animal studies for the treatment of SCIs.

Practical Implications

Therapeutic Target

The JAK/STAT pathway represents a potential therapeutic target for spinal cord injury, offering possibilities for developing small-molecule inhibitors.

Personalized Medicine

Understanding disease heterogeneity and molecular patterns is needed to predict the best therapeutic approaches for individual SCI patients, supporting the development of personalized medicine strategies.

Drug Development

Further research and clinical trials are needed to optimize therapies, understand disease mechanisms, and drug modes of action to support patient selection and treatment stratification.

Study Limitations

1
The temporal or spatial alterations of STATE after SCIs have not been fully elucidated.
2
The mechanisms that drive disease heterogeneity among and within patients have remained poorly-understood, which greatly limits our ability to predict the best therapies for patients or responses to those therapies.
3
Although cytokines and JAKs are involved in immune rejection, the extent of inhibition, speciﬁc target sites and the speciﬁc roles of individual JAKs need to be further investigated.

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