Functions and Therapeutic Potential of Extracellular Hsp60, Hsp70, and Hsp90 in Neuroinflammatory Disorders
, Alessandra Maria Vitale 1, Celeste Caruso Bavisotto 1, Everly Conway de Macario 2, Claudia Campanella 1, Alberto J. L. Macario 2,3 and Antonella Marino Gammazza 1,*
Round 1
Reviewer 1 Report
The authors present an interesting review about the function and therapeutic potential of molecular chaperones (Hps60, 70 and 90) in neuroinflammatory disorders, focusing on Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis.
Regarding the references they cite, most of them are recent, including articles from 2020.
They describe how the same chaperone could have different effect depending, for example, whether acts extracellular or intracellular level. Also, the authors detail the effect of Hsp’s on neurons and neuroglia.
Suggestions:
1. I suggest doing a table including the neurodegenerative diseases and the function (e.g. pro or antiinflamatory, extra or intreacellular, etc) of Hsp 60, 70 and 90, like:
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Hsp 60 |
Hsp 70 |
Hsp 90 |
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AD |
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PS |
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HD |
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MS |
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ALS |
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2. Also could be useful to add, if possible, a table of abbreviations used in the article.
3. Line 202: NFTs instead NTFs.
Author Response
Thank you very much for the positive comments. We modified the text according to the suggestions. Please see the attached revised version of the manuscript.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Alberti and collegues wrote a review about the interesting role of extracellular chaperones in the onset of neuroinflammatory diseases of central nervous system through their involvement in immune-system modulation. This review was well structured in two main sections. The first was focused on the immunomodulatory function of ex-HSPs where the authors analyzed synthetically, but in an exhaustive manner, the different ways by which Hsp90, Hsp70 and Hsp60 can modulate the innate immune response. It could be interesting if the authors will make a short mention about the extracellular localization of TRAP1 chaperone (Hsp75) and its potential role in immune-system regulation, due to its involvement in Parkinson’s disease, clearly in case of literature evidences about these topics. Instead, in the second section the neuroinflammation contribution to the CNS diseases was investigated with several references on the extracellular HSPs’ involvement in these pathological processes. I would suggest to authors to split this section in subparagraphs, one for each evaluated neurodegenerative diseases-neuroinflammation, for a better reading of manuscript.
In my opinion it could be interesting also to refer to some “chaperone therapies” in preclinical or clinical trials (i.e. Arimoclomol) for neurodegenerative disorder management, in order to add value to the manuscript.
Overall, the manuscript is well written, even if some minor stylistic revisions should be made (line 95, 103, 114, 128, 129, 141, 170, 219, 232, 276,319, check the space between words).
I think this review is acceptable for publication in Applied Sciences journal.
Author Response
Thank you very much for the positive comments. We have corrected the typographic and grammatical errors and revised our manuscript according to the suggestions. Please see the attached revised version of the manuscript.
Author Response File: Author Response.docx
