Submited on: 03 Nov 2011 05:48:43 PM GMT
Published on: 04 Nov 2011 07:17:25 AM GMT
 
Toll-like Receptors and Prion Disease: Relevance to Pathology and Novel Therapy
Posted by Dr. Trey Warnock on 03 Nov 2017 05:23:58 AM GMT Reviewed by Interested Peers

  • What are the main claims of the paper and how important are they?

    This review article lead (and ended) with the claim that immune response to priod diseases is potentially innervated throught the Toll-like receptor pathway. This is an interesting approach to the pathological response from prion diseases. This claim would suggest the response is similar that of a bacterial infection or virus.


  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    Buidling off of the previous section, this is a novel concept because it would lead one to believe that the response to an stimulus response is the same. However, the caveat to this though is that the author alludes to several studies citing that this pathay that prion diseases innervate through are MyD88 independent, meaning that the adapted response to something like this may be slim to none.


  • Are the claims properly placed in the context of the previous literature?

    This is a review article, the whole premise of this type of artcile is talk about Toll-like receptors and prion disease in suffieciently cited and researched manner. Therefore the claims are properly placed.


  • Do the results support the claims? If not, what other evidence is required?

    The information leads one to conclude that prion diseases may innervate through the Toll-like receptor cascade.


  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    N/A


  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    N/A


  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    This is an excellent foundational review article for something in this field in particular. The author was very thorough in the information presentated. The only comment was only the one mentioned earlier.


  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    This is a thought provoking hypothesis generating article; however, I would not call it practice artering. It may make us think a bit more critically on how the innate immune system adapts to a given stimuli.


  • Other Comments:

    Other than pieces of the article being a bit wordy, everything else was very thorough and well explained. Future elaboration on the prion disease would another foundational layer to this story the author is trying to depict.

  • Competing interests:
    .
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    No
  • References:
    None
  • Experience and credentials in the specific area of science:

    Experience none. Knowledge, yes. I have a PharmD background; therefore, I can comment on the need for more information compilation like this is.

  • How to cite:  Warnock T .Toll-like Receptors and Prion Disease: Relevance to Pathology and Novel Therapy[Review of the article 'Toll-like Receptors (TLRs) and Prion Disease: Relevance to Pathology and Novel Therapy ' by Ofodile O].WebmedCentral 2017;8(11):WMCRW003392
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1 Is the subject of the article within the scope of the subject category? Yes
2 Are the interpretations / conclusions sound and justified by the data? Partly
3 Is this a new and original contribution? Yes
4 Does this paper exemplify an awareness of other research on the topic? Yes
5 Are structure and length satisfactory? No
6 Can you suggest brief additions or amendments or an introductory statement that will increase the value of this paper for an international audience? Yes
7 Can you suggest any reductions in the paper, or deletions of parts? Yes
8 Is the quality of the diction satisfactory? No
9 Are the illustrations and tables necessary and acceptable? No
10 Are the references adequate and are they all necessary? Yes
11 Are the keywords and abstract or summary informative? No
  • Other Comments:

    Are the interpretations / conclusions sound and justified by the data? Throughout the text, a line of reasoning is developed that is  partly supported by the literature cited. The author makes a clear case for: a) the shortcomings of the prion hypothesis, and the need to thoroughly investigate alternative models of ethiopathogenesis for TSE; b) the role of neuroinflammation in neurodegeneration, and the sharing of biochemical mechanisms between TSE and AD; c) the important role of TLR, in the CNS and elsewhere, in driving protective as well as pathogenic, inflammatory and innate immune responses; d) the association between soluble components of the host response to infection, such as CRP and pentraxins, and the pathogenesis of TSE, as well as the roles of TLR; e) the properties of PrP that make it likely a player in oxidative stress and copper toxicity; f) the existence of suggestive evidence linking a variety of conventional microbial agents to the pathogenesis of TSE, most likely as a co-factor with PrP. However, the reasoning presents a number of weaknesses: a) no definitive association of a bacterial pathogen to TSE is as yet  accepted by most workers in the field; b) evidence of benefit arising from conventional antimicrobial treatment in TSE is contradictory and/or insufficient; c) there is no articulate hypothesis to link a conventional microbial pathogen and PrP, even if TLR are taken into account, which I am willing to grant. All of these should not obscure the fact that an important mass of published work is referenced and analysed in the review, which is useful to those willing to approach the subject. 

    Are structure and length satisfactory? Can you suggest brief additions or amendments or an introductory statement that will increase the value of this paper for an international audience? Can you suggest any reductions in the paper, or deletions of parts? This paper is difficult to read, not only because of numerous repetitions, but most importantly, by a number of typos, some of which delete or alter essential information (see lever for liver, for instance). Furthermore, there are factual errors in the analysis, such as the confusion between mycoplasmas and mycobacteria, which is a serious mistake from a microbiological point of view. Description of TLR biology is also fraught with hasty generalizations, such as the idea that all TLR present in a given cell type have the same specificity. Thorough review of the text, correction of typos and ommissions, adequate referencing (for instance, a paper of 2001 by a group for which many other subsequent references are provided is referred to as recent evidence), and checking of basic facts in microbiology, biochemistry and pathology are all essential for making this article adequate for a wider readership. I suggest reducing the length of the text by one-third, with no change in the reference  list.

    Is the quality of the diction satisfactory? Are the keywords and abstract or summary informative? There are many parts that need complete revision as to current English usage and ortograph. The abstract tells the reader very little about the main idea, namely that TSE are inflammatory diseases leading to neurodegeneration, and therefore if TLR can be proven to drive its neurodegenerative mechanisms, interventions targeting TLR and associated cellular mechanisms (oxidative stress, lipid raft assembly, cholesterol metabolism) might be of benefit to the patients, either alone or in association with antimicrobial and immunomodulatory strategies. Please note that all of this key message deserves the reader's attention, but is lost in the current structure of the abstract, as well as in the fuzzy style of the main text.

  • Competing interests:
    None at all
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    No
  • References:
    None
  • Experience and credentials in the specific area of science:

    I have been carrying out research in immunological mechanisms of disease for the last 25 years, with a focus on cytokine regulation and models of allergic disease. I have no direct experience in the TSE field, but I know what a well-written review should look like, and this paper needs some work before it reaches that level.

  • How to cite:  Xavier-Elsas P .WMC002410 Toll-like receptors in prion diseases - suggestions and comments[Review of the article 'Toll-like Receptors (TLRs) and Prion Disease: Relevance to Pathology and Novel Therapy ' by Ofodile O].WebmedCentral 2017;2(11):WMCRW001133
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1 Is the subject of the article within the scope of the subject category? Partly
2 Are the interpretations / conclusions sound and justified by the data? Partly
3 Is this a new and original contribution? No
4 Does this paper exemplify an awareness of other research on the topic? Yes
5 Are structure and length satisfactory? No
6 Can you suggest brief additions or amendments or an introductory statement that will increase the value of this paper for an international audience? Yes
7 Can you suggest any reductions in the paper, or deletions of parts? Yes
8 Is the quality of the diction satisfactory? Yes
9 Are the illustrations and tables necessary and acceptable? Yes
10 Are the references adequate and are they all necessary? Yes
11 Are the keywords and abstract or summary informative? Yes
  • Other Comments:

    1. There is a good amount of deviation from the main concept of the review namely TLR-Prion, particularly in the abstract and conclusion.  The necessary corrections have been put in the track changes and the same is forwarded to the editor.

    2. Data in the form of tables, graphs and figures are not given. They are must in this type of long review to appreciate the statements.

    5. The length need to be reduced in the other sections also.

    6. With regard to the abstract and conclusion, I made some changes and the type mistakes are also shown in the track changes.

    7. Done

    9. Tables and illustrations are not given. Author has to make a few.

    10. The recent the 2011 Nobel Prize is on TLRs.  One of the Noble laurate work was quoted Dr. Hoffmann and another Noble laurate Bruce A  Beuter work also need to be cited. Also the author did mention about the Dendritic cells.   Ralph m Steinman who discovered dendrtic cell and his work  need to be cited.

     

  • Competing interests:
    no, I shall be submitting the track changes separately to the editor
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    No
  • References:
    None
  • Experience and credentials in the specific area of science:

    My experience is with TLR polymorphism. I did not have exposure in Prions

  • How to cite:  Sreerama K .Toll-like Receptors (TLRs) and Prion Disease: Relevance to Pathology and Novel Therapy [Review of the article 'Toll-like Receptors (TLRs) and Prion Disease: Relevance to Pathology and Novel Therapy ' by Ofodile O].WebmedCentral 2017;2(11):WMCRW001120
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1 Is the subject of the article within the scope of the subject category? Yes
2 Are the interpretations / conclusions sound and justified by the data? Yes
3 Is this a new and original contribution? Yes
4 Does this paper exemplify an awareness of other research on the topic? Yes
5 Are structure and length satisfactory? Yes
6 Can you suggest brief additions or amendments or an introductory statement that will increase the value of this paper for an international audience? No
7 Can you suggest any reductions in the paper, or deletions of parts? No
8 Is the quality of the diction satisfactory? No
9 Are the illustrations and tables necessary and acceptable? Yes
10 Are the references adequate and are they all necessary? No
11 Are the keywords and abstract or summary informative? Yes
  • Other Comments:

    8. There are some typing errors:


    1. Page 4, last paragraph of Introduction: pattern-recognition receptors (PRP).

     

    2. Page 9, last left paragraph: Denditic cells have …

     

    3. Page 10, last left paragraph: gene targets to and generate …

     

    4. Page 15, last left paragraph: variety of micobial cell-wall components …

     

     

    10. The references are outdated, missing from 2009-2011.

     

     

     

  • Competing interests:
    No
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    No
  • References:
    None
  • Experience and credentials in the specific area of science:

     

    I taught for 9 years of Medical Microbiology Course for residents of the sub-specialty in Infectious Diseases, National Medical Center "La Raza" in Mexico City.

     

  • How to cite:  Garcia G .Toll-like receptors(TLRs) and prion disease: relevance to pathology and novel therapy.[Review of the article 'Toll-like Receptors (TLRs) and Prion Disease: Relevance to Pathology and Novel Therapy ' by Ofodile O].WebmedCentral 2017;2(11):WMCRW001103
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