The Pharmacological Potential of Adenosine A_2A Receptor Antagonists for Treating Parkinson’s Disease

Round 1

Reviewer 1 Report

In this manuscript, the authors reviewed the pharmacology of adenosine A2A receptor antagonists from the perspective of the treatment of both motor and non-motor symptoms of PD and their potential for disease modification. In addition, they described the role of A2A receptors as a therapeutic target for other neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease and multiple sclerosis.

This review is interesting and well-written; unfortunately, the manuscript needs substantial improvements and corrections before publishing may be possible. As a review, it should give a more or less complete overview of the literature.

General points:

Please add a list of abbreviations before the References section to your manuscript.

For better readability, please add more Figures to your manuscript.

Special points:

Keywords

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Introduction

The Introduction section should be improved, i. e., by substantial references in the field:

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2. Adenosine A2A receptors and Parkinson’s disease

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2.2. Basal ganglia expression of A2A receptors

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2.3. Relevance of A2A receptor state to mechanism of action of adenosinergic agents in managing 146 the motor symptoms of Parkinson’s disease

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Clinical actions of adenosine A2A antagonists in Parkinson’s disease

3.1. Motor symptoms

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3.2. Non-Motor Symptoms

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3.2.1. Role of A2A receptors in sleep-wake cycle disturbance

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3.2.3. Role of A2A receptors in mood disorders

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3.3. Role of A2A receptors in cognitive impairment

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5. Summary and conclusions

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Box 1. Adenosine A2A receptors in other neurological diseases

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Adenosine A2A receptors and neurological disease

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Legend Figure 1

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Author Response

Please see attachment (for easier reading)

Author Response File: Author Response.pdf

Reviewer 2 Report

The review “The Pharmacological Potential of Adenosine A2A Receptor Antagonists for Treating Parkinson’s Disease” by Mori et al., explores the role of Adenosine A2a receptor in PD. The review is well written and covers all aspects of PD associated with the A2a receptor.

The manuscript can be accepted for publication. 

Author Response

We thank the reviewer for their kind comments. 

Reviewer 3 Report

The paper by Mori et al., is an excellent review of the pharmacological evidence underlying the use of A2A adenosine receptor antagonists for the treatment of both motor and non-motor symptoms of Parkinson’s Disease, as well as their potential as disease-modifying therapy. The authors concisely summarize all the crucial information regarding the preclinical and clinical pharmacology of A2A adenosine receptor antagonists, supporting their role as a target not only for Parkinson’s Disease but also for other neurodegenerative diseases and neuropsychiatric disorders.

Author Response

We thank the reviewer for their kind comments

Reviewer 4 Report

I have carefully read the review by Mori et al. The paper offers a comprehensive overview of A2a receptor antagonists effects in Parkinosn's disease. The review is well organized and written and may be of interest for purinergic scientists.

Minor:

Please add the reference by Merighi et al., 2021 about expression of A2A receptors in brain and platelets of patients with Alzheimer's disease.

Author Response

We thank the reviewer for their kind comments, and have added the requested reference.  

Round 2

Reviewer 1 Report

The authors did a really good job - all my critical points have been successfully adressed.  I have no further suggestions or concerns.