C-C Motif Chemokine Ligand 2 and Chemokine Receptor 2 in Cardiovascular and Neural Aging and Aging-Related Diseases

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

Reviewer Comments

1.       The reviewer is unsure whether the authors are indicating that elevated β-amyloid levels induce CCL2 expression, induce infiltration, or result from migration. If this interpretation cannot be made, please address this point in the discussion for clarification.

2.       Please elaborate on the mechanisms through which chemokines initiate intracellular signaling cascades that facilitate chemotaxis, degranulation, actin rearrangement, and the release of superoxide anions.

3.       What is the current understanding of CCL2-CCR2 expression in age-related cognitive decline, myocardial conditions, and the activation of proinflammatory macrophages?

4.       Explain the significant role of CCR2 (CD192) in biological processes involving monocytes/macrophages and lymphocytes.

5.       CCR2-positive monocytes are suggested to be powerful regulators of central nervous system inflammation, contributing to neuronal demyelination and disease progression in later stages?

6.       Does this suggest that the CCL2 protein may have additional functions, or that even minor changes are significant for altering signaling through these MMP-12 receptors?

7.       Are there any other binding regions in the C-C chemokines typically associated with C-C chemokine receptor activity? This group could also be interesting to assess for receptor utilization.

 

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

 

The present review provides interesting and well documented evidence of the relevant biological role played by the CCL2- CCR2 axis in cardiovascular and, generally, in aging related diseases. The introduction clearly introduces the theme of aging and its progression including the role played by chemokines. The working axis CCL2- CCR2 is exhaustively described and relevant data quoted and discussed. In addition, the future possibility to therapeutically modulate this axis to cope with various aging-related diseases is critically explored and advantages and disadvantages well pointed out.

Author Response

We sincerely thank the reviewer for the time and efforts dedicated to reviewing our manuscript and appreciate the positive comments and praise on this review.