Leveraging the ATP‐P2X7 receptor signalling axis to alleviate traumatic CNS damage and related complications

Abstract The P2X7 receptor is an exceptional member of the P2X purinergic receptor family, with its activation requiring high concentrations of extracellular adenosine 5ʹ‐triphosphate (ATP) that are often associated with tissue damage and inflammation. In the central nervous system (CNS), it is highly expressed in glial cells, particularly in microglia. In this review, we discuss the role and mechanisms of the P2X7 receptor in mediating neuroinflammation and other pathogenic events in a variety of traumatic CNS damage conditions, which lead to loss of neurological and cognitive functions. We raise the perspective on the steady progress in developing CNS‐penetrant P2X7 receptor‐specific antagonists that leverage the ATP‐P2X7 receptor signaling axis as a potential therapeutic strategy to alleviate traumatic CNS damage and related complications.

Dear Prof A Hargrove, Many thanks for your kind consideration of our proposal of writing a review manuscript for MRR.
The P2X7 receptor is an important molecular mechanism mediating inflammation of tissues including the CNS and, not surprisingly, it has been identified as an attractive anti-inflammation target.MRR has recently published a review on this interesting topic, focusing on in neuroinflammation in neurodegenerative diseases (Calzaferri F, Ruiz-Ruiz C, de Diego AMG, de Pascual R, Méndez-López I, Cano-Abad MF, Maneu V, de Los Ríos C, Gandía L, García AG (2020) The purinergic P2X7 receptor as a potential drug target to combat neuroinflammation in neurodegenerative diseases, Med Res Rev, 40(6):2427-2465).This review have omitted by large the recent groundbreaking works (e.g., McCarthy AE, Yoshioka C, Mansoor SE (2019) Full-Length P2X(7) Structures Reveal How Palmitoylation Prevents Channel Desensitization, Cell, 179(3):659-670.e13),which inform the structural basis for the modus operandi of the P2X7 receptor.This paper has not touched on the recent progress in revealing the critical role of P2X7-mediated neuroinflammation in multiple traumatic CNS damage, which are, albeit less prevalent, equally or arguably more debilitating than neurodegenerative diseases, and the promising perspective on the use of CNS-penetrant P2X7 antagonists as a therapeutic strategy for such conditions.The lack of the recent developments on these important forefronts has compelled us to propose writing this review manuscript.As a reader and as a reviewer of MRR, I have come across quite a few papers including the above one on the P2X7 receptor by authors with a pretty thin track record on the research topic they are writing.We strongly believe that we are well or better qualified for the proposed review.

Lin-Hua Jiang
We have conducted an editorial evaluation and concluded that the proposed manuscript does not fit our publication plan.Because we receive far more manuscripts than we can possibly publish, we subject all manuscripts to an initial screening by considering many factors including timeliness of the manuscript, the level of activity of the field, author's level of expertise in the field as demonstrated by prior publications on the same subject, whether there have been recent reviews on the same subject as well as the need for the journal to publish manuscripts from diverse areas and diverse regions.
We wish you the very best in finding an appropriate journal for your interesting work and hope that you will consider Medicinal Research Reviews for future submissions.

Editor-in-Chief Medicinal Research Reviews
From: Microsoft Power Apps and Power Automate <microsoft@powerapps.com> Sent: Saturday, October 2, 2021 10:36 AM To: l.h.jiang@leeds.ac.uk <l.h.jiang@leeds.ac.uk>Cc: mrreditorial@wiley.com<mrreditorial@wiley.com> Subject: Your proposal entitled "Leveraging the role of the P2X7 receptor in neuroinflammation to mitigate traumatic CNS damage and support functional recoveryhas been submitted to Medicinal Research Reviews A new proposal has been submitted via Microsoft Forms from l.h.jiang@leeds.ac.uk.Proposal title: "Leveraging the role of the P2X7 receptor in neuroinflammation to mitigate traumatic CNS damage and support functional recovery" Article type: "Minireview Article" Corresponding author(s):"Lin-Hua Jiang" Corresponding author(s) affiliation(s):School of Biomedical Sciences, University of Leeds Outline: 1. Introduction 2. P2X7 receptor architecture and structural basis for ATP binding and receptor activation 3. Role of the P2X7 receptor in traumatic CNS damage and mechanisms for neuroinflammation 3.1 Spinal cord injury 3.2 Ischemic and haemorrhagic stroke 3.3 Hypoxiainduced neonatal seizures 3.4 Traumatic brain injury 3.5 Radiation-induced brain injury 3.6 Postoperative cognitive dysfunction 4. CNS-penetrant P2X7 receptor antagonists for imaging neuroinflammation and therapeutics 5. Concluding remarks and perspectives