Roles of SMAD and SMAD-Associated Signaling Pathways in Nerve Regeneration Following Peripheral Nerve Injury: A Narrative Literature Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript titled " Induction and roles of SMAD and SMAD-associated signaling pathways in nerve regeneration after peripheral nerve injury" provides a comprehensive overview of the role of SMAD signaling pathways in nerve regeneration, a critical topic for understanding and developing new therapeutic strategies for peripheral nerve damage. However, several aspects of the paper could benefit from further discussion to enhance its quality. 

·         The abstract could benefit from greater clarity and detail. It lacks essential information that clearly outlines the novelty and specific contributions of the study. It would be advisable to highlight which aspects of SMAD's role in nerve regeneration were investigated and which emerging results could transform the current understanding or treatment of peripheral nerve injuries.

·         The provided introduction is relatively brief and lacks context. Expanding this section to more thoroughly discuss the importance of nerve regeneration and the clinical implications of peripheral nerve injuries would be beneficial. It is essential to include an overview of the currently available therapies for repairing peripheral nerves, highlighting their limitations and failures, to further justify the need for exploring new therapeutic avenues such as those mediated by SMAD.

·         While the document discusses variations in SMAD expression following nerve injuries and associates these with potential outcomes in nerve regeneration, the mechanistic insights into how SMAD influences these processes remain superficial. A more in-depth investigation of the molecular mechanisms would provide stronger support for the conclusions drawn.

·         The conclusion of the work could be further improved by including a discussion on the clinical relevance of the findings, highlighting how SMAD signaling pathways could be exploited to develop new therapies. Clarifying how the study's results could be translated into potential treatments or how they might influence the current understanding of nerve regeneration and degeneration would provide significant added value.

·         The authors should ensure that all citations and bibliographical references are standardized.

 

·         A careful review of the English language is recommended.

Comments on the Quality of English Language

·       A careful review of the English language is recommended.

Author Response

"Please see the attachment."

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This is a very well written manuscript, centered on an effort to review all avaialable bibliographic search centered on periphreral nerve regeneration after traumatic axonal injury.

This thematic unit represents a really interesting theme, which intereferes with neurosurgery, orthopedic surgery and molecular biology. There is limited data available, as this entity represents a borderline between different medical subspecialities and the sample size of any relevant studies is limited. 

The data presented are precisely collected and the majority of relevant references is presented. The presentation of the study is of high quality and all important points of interest are highlighted. The objective of the study was to summarize our knowledge and to potentially elucidate the roles of SMADs in nerve degeneration and regeneration after nerve injury. And, according to my opnion, this is adequately accomplished.

The only correction that should be included is rerelated with the title of the manuscript. A phrase such as 'a narrative literature review' should be included in order to further declare the scope of the manuscript. 

 

Comments on the Quality of English Language

I strongly consider that minor editing of English language is required.

Author Response

"Please see the attachment."

Author Response File: Author Response.pdf