The Role of Lysophosphatidic Acid in Neuropsychiatric and Neurodegenerative Disorders

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dedoni et al. reviewed the role of Lysophosphatidic Acid in neuropsychiatric and neurodegenerative Disorders. The authors nicely described the role of LPA in neurological disorders and is well organized.

I have some minor concerns that need to be addressed before publication

1.      Authors should extensively explain structure, function, metabolism, and Lysophosphatidic Acid.

2.      Authors should also discuss Lysophosphatidic Acid receptors and their signaling mechanism with Lysophosphatidic Acid.

3.      Using recent publications and patents, the drug development significance of LPA should also be included.

4.      The conclusion should be more elaborated.

 

5.      Typo and grammatical errors should be removed.

Comments on the Quality of English Language

Minor editing of English language required

Author Response

Referee 1

We thank the Reviewer for the positive comments.

Comments and Suggestions for Authors

Dedoni et al. reviewed the role of Lysophosphatidic Acid in neuropsychiatric and neurodegenerative Disorders. The authors nicely described the role of LPA in neurological disorders and is well organized.

I have some minor concerns that need to be addressed before publication

1. Authors should extensively explain structure, function, metabolism, and Lysophosphatidic Acid.

We appreciate the suggestion and have made the changes recommended by the referee. To improve the review, we added a paragraph (2. LPA and LPA receptors: an overview); However, we would like to underline that our initial objective was to emphasize and focus attention on the possible involvement of LPA in neuropsychiatric and neurodegenerative disorders and we had intentionally chosen not to go into the "history of LPA", both because there are already countless reviews online that thoroughly investigate this aspect, but above all we wanted to focus the reader’s attention on the main topic of the review. Nonetheless, we welcomed the idea, and the necessary changes were made.

2. Authors should also discuss Lysophosphatidic Acid receptors and their signaling mechanism with Lysophosphatidic Acid.

Thanks for the suggestion. To improve the review, we added a paragraph to include what was requested by the referee.

3. Using recent publications and patents, the drug development significance of LPA should also be included.

Some information regarding the drug development of LPA was included in the conclusions.

4. The conclusion should be more elaborated.

The conclusions were modified, as suggested by the referee.

5. 5.      Typo and grammatical errors should be removed.

 A detailed check of typos and grammatical errors was performed.

Reviewer 2 Report

Comments and Suggestions for Authors

A review of the manuscript titled „ The Role of Lysophosphatidic Acid in Neuropsychiatric and Neurodegenerative Disorders” by S. Dedoni, C. Camoglio, C. Siddi, M. Scherma, W. Fratta, and P. Fadda submitted to Future Pharmacol.

In the manuscript, the authors discuss the involvement of lysophosphatidic acid (LPA) in neuropsychiatric and neurodegenerative disorders in light of the most recent studies, to better understand these diseases and try to give innovative future treatments.

The work is interesting, but in its current form, due to the length of individual chapters, it is quite difficult to read and understand.

Please reconsider the following:

1. Distinguish the results of clinical studies from experimental ones in individual chapters.

2. Isolate the pharmacological modulation of lysophosphatidic acid concentration

3. The authors present the formation and mechanism of action of lysophosphatidic acid, but there is no concise description of its action in the body. I propose to clearly state the meaning of this relationship.

 

4. It is worth clearly emphasizing the importance of lysophosphatidic acid in the future.

Author Response

Referee 2

We thank the Reviewer for the positive comments.

A review of the manuscript titled „ The Role of Lysophosphatidic Acid in Neuropsychiatric and Neurodegenerative Disorders” by S. Dedoni, C. Camoglio, C. Siddi, M. Scherma, W. Fratta, and P. Fadda submitted to Future Pharmacol.

In the manuscript, the authors discuss the involvement of lysophosphatidic acid (LPA) in neuropsychiatric and neurodegenerative disorders in light of the most recent studies, to better understand these diseases and try to give innovative future treatments.

The work is interesting, but in its current form, due to the length of individual chapters, it is quite difficult to read and understand.

Please reconsider the following:

1. Distinguish the results of clinical studies from experimental ones in individual chapters.

The results of clinical studies were isolated from experimental ones in individual chapters as suggested by the referee.

2. Isolate the pharmacological modulation of lysophosphatidic acid concentration

Thank you for your suggestion. We included some information in the conclusions.

3. The authors present the formation and mechanism of action of lysophosphatidic acid, but there is no concise description of its action in the body. I propose to clearly state the meaning of this relationship.

Thank you for your advice. Subchapter 2.1 now includes a discussion of the effects of LPA and its receptors in the organism.

4. It is worth clearly emphasizing the importance of lysophosphatidic acid in the future.

Thank you for your suggestion. The importance of lysophosphatidic acid in the future was also included in the conclusions.

Reviewer 3 Report

Comments and Suggestions for Authors

In the present manuscript entitled “The role of lysophosphatidic acid in neuropsychiatric and neurodegenerative disorders”, Dedoni et al, summarized the essential roles of the well-known phospholipid, LPA in neuropsychiatric and neurodegenerative disorders, including schizophrenia, depression, Alzheimer and multiple sclerosis. They discussed the potential of drugs that target the molecules on the LPA pathway as therapeutic agents for these diseases. They provided a lot of useful information for readers and gave hope for patients. Following are few concerns for this study.

 

Minor issues:

1)     In Figure 1, it’s easier to see if the arrow goes from top to bottom, so I think it is better to turn it upside down. In addition, it would be better to add cellular functions such as proliferation, migration, and differentiation at the bottom to explain what kind of physiological effects the LPA signaling pathways are ultimately involved in.

 

2)     Since there is a lot of information in Alzheimer’s disease’s chapter, it would be good to add a table or scheme that summarizes LPA subtypes and their signaling pathways in an easy-to -understand manner.

 

 

3)     The text “100 and 200 mM” on line 589 of page 13 is large, so please correct it.

Author Response

Referee 3

We thank the Reviewer for the positive comments.

In the present manuscript entitled “The role of lysophosphatidic acid in neuropsychiatric and neurodegenerative disorders”, Dedoni et al, summarized the essential roles of the well-known phospholipid, LPA in neuropsychiatric and neurodegenerative disorders, including schizophrenia, depression, Alzheimer and multiple sclerosis. They discussed the potential of drugs that target the molecules on the LPA pathway as therapeutic agents for these diseases. They provided a lot of useful information for readers and gave hope for patients. Following are few concerns for this study.

Minor issues:

• In Figure 1, it’s easier to see if the arrow goes from top to bottom, so I think it is better to turn it upside down. In addition, it would be better to add cellular functions such as proliferation, migration, and differentiation at the bottom to explain what kind of physiological effects the LPA signaling pathways are ultimately involved in.

We have modified the figure as suggested by the referee.

 

2)     Since there is a lot of information in Alzheimer’s disease’s chapter, it would be good to add a table or scheme that summarizes LPA subtypes and their signaling pathways in an easy-to -understand manner.

We thank the reviewer for highlighting this point and we have now addressed this issue by adding a scheme that summarizes the LPA signaling pathways involved in Alzheimer’s disease.

3)     The text “100 and 200 mM” on line 589 of page 13 is large, so please correct it.

We're grateful for providing the suggestion, the text has been amended.

Reviewer 4 Report

Comments and Suggestions for Authors

This is a well-structured review article. The main question addressed by this review is the potential role of lysophosphatidic acid (LPA) in neuropsychiatric and neurodegenerative disorders.

The introduction gives the background of this study as it briefly describes neuropsychiatric and neurodegenerative disorders and LPA.

The main body of the review is quite interesting, well organized and nicely depicted in figures.

The conclusion is well written, summarizing the main findings of the review. However, I believe that the conclusion section could be enriched by the authors, perhaps including a paragraph with some limitations of the review and some specific targets for future studies too.

References are adequate in number and relative to the subject.

Comments on the Quality of English Language

English language and style are generally fine, with only minor issues to be addressed before publication.

Author Response

Referee 4

We thank the Reviewer for the positive comments.

This is a well-structured review article. The main question addressed by this review is the potential role of lysophosphatidic acid (LPA) in neuropsychiatric and neurodegenerative disorders. The introduction gives the background of this study as it briefly describes neuropsychiatric and neurodegenerative disorders and LPA. The main body of the review is quite interesting, well organized and nicely depicted in figures. The conclusion is well written, summarizing the main findings of the review. However, I believe that the conclusion section could be enriched by the authors, perhaps including a paragraph with some limitations of the review and some specific targets for future studies too.

Thank you for your suggestion. We enriched the conclusion paragraph adding some more information as suggested by the referee.

References are adequate in number and relative to the subject.

Comments on the Quality of English Language: English language and style are generally fine, with only minor issues to be addressed before publication.

 

Reviewer 5 Report

Comments and Suggestions for Authors

Authors have undertaken  the effort to summarized and  put things in order of the very interesting and important subject. Search for specific targets of therapy in neuropsychiatric and neurodegenerative disorders  is of centre of interest considering complicated, difficult  and mental disease prone everyday conditions of all World populations.  Manuscript is well written and inculdes all kind of available data considering in vivo and in vitro human and animal most recent investigations and discoveries,  with well prepared molecular interaction schemes that make  content of manuscript more easy to assimilate. Various molecular  receptors, pathways and their interactios are clearly and prcisely described . That is important  particularly for clinicists. All proper references are included and discussed. Particularly valuable and new is part  3. „LPA Involvement in Minor Neuropsychiatric Disorders”. Conclusions  demonstrating the role of LPA as an active mediator in neuropsychiatric and neurodegenerative illnesses are well documented . Manuscript can be published in present form.

Author Response

Referee 5

Authors have undertaken  the effort to summarized and  put things in order of the very interesting and important subject. Search for specific targets of therapy in neuropsychiatric and neurodegenerative disorders  is of centre of interest considering complicated, difficult  and mental disease prone everyday conditions of all World populations.  Manuscript is well written and inculdes all kind of available data considering in vivo and in vitro human and animal most recent investigations and discoveries,  with well prepared molecular interaction schemes that make  content of manuscript more easy to assimilate. Various molecular  receptors, pathways and their interactios are clearly and prcisely described . That is important  particularly for clinicists. All proper references are included and discussed. Particularly valuable and new is part  3. „LPA Involvement in Minor Neuropsychiatric Disorders”. Conclusions  demonstrating the role of LPA as an active mediator in neuropsychiatric and neurodegenerative illnesses are well documented . Manuscript can be published in present form.

We appreciate the referee's pleasant comments.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

In its current form, the manuscript is ready for publication.