Neuroglia in Neurodegeneration: Exploring Glial Dynamics in Brain Disorders
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe role of neuroglia in health and disease is a very hot topic. The authors focus on the complex interactions between different glial cell types and neurons, highlighting recent discoveries in glial-neuronal metabolic coupling, neuroinflammation, and protein aggregation. They also discuss emerging concepts in neuroglial research, including the role of extracellular vesicles in disease propagation, epigenetic regulation of glial function, and the application of artificial intelligence in glial biology. Finally, they summarize the therapeutic implications of targeting glia in neurodegenerative diseases, addressing both the promising avenues and challenges in developing glial-focused interventions. The manuscript is well written and the language flows smoothly.
My major comments:
1. As a comprehensive review, I suggest the authors to provide more detailed studies regarding the mechanism underlying the glia-glia interaction and glia-neuron interaction in neurodegenerative diseases.
2. I suggest the authors to rearrange the structure so that the logic of each section is clearer.
3. References should be updated to include more recent studies that have been published within 3 years.
Author Response
Reviewer 1
The role of neuroglia in health and disease is a very hot topic. The authors focus on the complex interactions between different glial cell types and neurons, highlighting recent discoveries in glial-neuronal metabolic coupling, neuroinflammation, and protein aggregation. They also discuss emerging concepts in neuroglial research, including the role of extracellular vesicles in disease propagation, epigenetic regulation of glial function, and the application of artificial intelligence in glial biology. Finally, they summarize the therapeutic implications of targeting glia in neurodegenerative diseases, addressing both the promising avenues and challenges in developing glial-focused interventions. The manuscript is well written and the language flows smoothly.
My major comments:
Query 1. As a comprehensive review, I suggest the authors provide more detailed studies regarding the mechanism underlying the glia-glia interaction and glia-neuron interaction in neurodegenerative diseases.
Response: We thank you for your valuable comment. In response, we have extensively revised sections 5-9, which cover glia-glia and glia-neuron interactions, providing additional details on the underlying mechanisms in neurodegenerative diseases. These revisions are highlighted in red in the revised manuscript.
Query 2. I suggest the authors rearrange the structure so that the logic of each section is clearer.
Response: Thank you for your thoughtful feedback. We have restructured the manuscript to enhance the clarity and flow of the discussion. Each section has been carefully organized to provide a cohesive overview of neuroglia in neurodegeneration. We have dedicated sections for each major glial cell type (astrocytes, microglia, and oligodendrocytes) to ensure a systematic exploration of their roles in both neuroprotection and neurodegeneration. We believe this restructuring strengthens the narrative and enhances the overall clarity of the review.
Query 3. References should be updated to include more recent studies that have been published within the last 3 years.
Response: We appreciate your suggestion. We have revised the reference list to include several recent studies published within the last three years. This update ensures the manuscript reflects the latest findings in the field and maintains its relevance to current research trends.
Reviewer 2 Report
Comments and Suggestions for AuthorsThis is an absolutely timely contribution to the field. The paper is well written, consciously orginized and cites numerous important references to the field. As reading through the paper I have one general but important remark to make.
The paper very often stays on the surface of the topic, it does not scratch the bottom of the problems. To make cleat my opinion let me give a few examples:
Chapter 7. last sentence: "Oligodendrocyte-drived exosomes cen modulate microglial activation highlighting the bidirectional nature of this interaction" - the autjors leave us with doubts, what bidirectiobnal exactly means in this case?
Chapter 9. Grub,an et al......REVEALING COMPLEX INTERACTIONS BETWEEN DIFFERENT GLIAL CELL TYPES... - again, thereis nothing about the nature abozt these interactions.
Chapter 11C: .".. the dual role of EV1Sboth exacerbating and mitigating disease.." - again nodetails given. What takes the processes one way and the and the oether?
Chapter 11D: last sentence: "Epigenetic ecahnismsmay also be crucial for developing.." - again, there is no support fo this claim.
The paper is full with such notons without explnation or supporting thopughts. It is not enough to cte references at these points, the authors should shortly comments thoase and explain the essence for the readers.
At the end, Chapter 14 is full with very generalized and NOT useful future directions. It is well known for long that the inportance of "optimal therapeutic window", the "combination therapies" and oersonalized midicuine" are important buzzwords for research. Please support these claims with motre concreta suggestions.
Author Response
Reviewer 2
This is an absolutely timely contribution to the field. The paper is well written, consciously organized, and cites numerous important references in the field. As I read through the paper, I have one general but important remark to make. The paper very often stays on the surface of the topic; it does not scratch the bottom of the problems. To make clear my opinion, let me give a few examples:
Chapter 7, last sentence: "Oligodendrocyte-derived exosomes can modulate microglial activation, highlighting the bidirectional nature of this interaction." - the authors leave us with doubts about what "bidirectional" exactly means in this case.
Response: We thank you for pointing this out. We have revised this section to provide a clearer explanation of the bidirectional interaction between oligodendrocyte-derived exosomes and microglial activation. These changes are highlighted in red in the revised manuscript.
Chapter 9, Grub, et al.: "REVEALING COMPLEX INTERACTIONS BETWEEN DIFFERENT GLIAL CELL TYPES..." - again, there is nothing about the nature of these interactions.
Response: We appreciate your comment and have thoroughly revised this section to elaborate on the nature of the complex interactions between different glial cell types. These revisions are now clearly marked in red in the updated manuscript.
Chapter 11C: "The dual role of EV is both exacerbating and mitigating disease..." - again, no details are given. What drives these processes in different directions?
Response: We have carefully addressed this query by expanding the explanation of how EV can both exacerbate and mitigate disease. The revised section now provides more detailed information about the mechanisms that determine the outcome of these processes. These changes are highlighted in red in the manuscript.
Chapter 11D, last sentence: "Epigenetic mechanisms also be crucial for developing..." - again, there is no support for this claim.
Response: We thank you for your feedback. We have revised this section to include supporting details on the role of epigenetic mechanisms in neurodegenerative disease development. The changes are highlighted in red in the revised manuscript.
The paper is full of such notions without explanation or supporting thoughts. It is not enough to cite references at these points; the authors should briefly comment on them and explain the essence for the readers.
Response: We greatly appreciate your insightful comment. In response, we have thoroughly revised the manuscript to provide more detailed explanations for the statements that previously lacked sufficient context. These revisions aim to clarify the essence of each notion and provide a deeper understanding for the readers. The changes are clearly marked in red.
At the end, Chapter 14 is full of very generalized and NOT useful future directions. It is well known for long that the importance of the "optimal therapeutic window," "combination therapies," and "personalized medicine" are important buzzwords for research. Please support these claims with more concrete suggestions.
Response: We appreciate your constructive criticism regarding the future directions section. In response, we have revised the entire section to provide more specific, actionable suggestions for addressing the challenges in glial-targeted therapies. The revised version offers a more concrete outlook on optimizing therapeutic windows, combination therapies, and personalized medicine in neurodegeneration. These changes are highlighted in red in the revised manuscript.
