Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury
Traumatic spinal cord injury (SCI) is characterized by severe neuroinflammation and hampered neuroregeneration, which often leads to permanent neurological deficits. Current therapies include decompression surgery, rehabilitation, and in some instances, the use of corticosteroids. However, the golde...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8135 |
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| author | Femke Mussen Jana Van Broeckhoven Niels Hellings Melissa Schepers Tim Vanmierlo |
| author_facet | Femke Mussen Jana Van Broeckhoven Niels Hellings Melissa Schepers Tim Vanmierlo |
| author_sort | Femke Mussen |
| collection | DOAJ |
| description | Traumatic spinal cord injury (SCI) is characterized by severe neuroinflammation and hampered neuroregeneration, which often leads to permanent neurological deficits. Current therapies include decompression surgery, rehabilitation, and in some instances, the use of corticosteroids. However, the golden standard of corticosteroids still achieves minimal improvements in functional outcomes. Therefore, new strategies tackling the initial inflammatory reactions and stimulating endogenous repair in later stages are crucial to achieving functional repair in SCI patients. Cyclic adenosine monophosphate (cAMP) is an important second messenger in the central nervous system (CNS) that modulates these processes. A sustained drop in cAMP levels is observed during SCI, and elevating cAMP is associated with improved functional outcomes in experimental models. cAMP is regulated in a spatiotemporal manner by its hydrolyzing enzyme phosphodiesterase (PDE). Growing evidence suggests that inhibition of cAMP-specific PDEs (PDE4, PDE7, and PDE8) is an important strategy to orchestrate neuroinflammation and regeneration in the CNS. Therefore, this review focuses on the current evidence related to the immunomodulatory and neuroregenerative role of cAMP-specific PDE inhibition in the SCI pathophysiology. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:16:30Z |
| publishDate | 2023-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bc60a633352f43da989a8cdfa49826cd2023-11-17T23:05:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249813510.3390/ijms24098135Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord InjuryFemke Mussen0Jana Van Broeckhoven1Niels Hellings2Melissa Schepers3Tim Vanmierlo4Department of Neuroscience, Biomedical Research Institute BIOMED, Hasselt University, 3590 Diepenbeek, BelgiumUniversity MS Center (UMSC) Hasselt-Pelt, Hasselt University, 3500 Hasselt, BelgiumUniversity MS Center (UMSC) Hasselt-Pelt, Hasselt University, 3500 Hasselt, BelgiumDepartment of Neuroscience, Biomedical Research Institute BIOMED, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Neuroscience, Biomedical Research Institute BIOMED, Hasselt University, 3590 Diepenbeek, BelgiumTraumatic spinal cord injury (SCI) is characterized by severe neuroinflammation and hampered neuroregeneration, which often leads to permanent neurological deficits. Current therapies include decompression surgery, rehabilitation, and in some instances, the use of corticosteroids. However, the golden standard of corticosteroids still achieves minimal improvements in functional outcomes. Therefore, new strategies tackling the initial inflammatory reactions and stimulating endogenous repair in later stages are crucial to achieving functional repair in SCI patients. Cyclic adenosine monophosphate (cAMP) is an important second messenger in the central nervous system (CNS) that modulates these processes. A sustained drop in cAMP levels is observed during SCI, and elevating cAMP is associated with improved functional outcomes in experimental models. cAMP is regulated in a spatiotemporal manner by its hydrolyzing enzyme phosphodiesterase (PDE). Growing evidence suggests that inhibition of cAMP-specific PDEs (PDE4, PDE7, and PDE8) is an important strategy to orchestrate neuroinflammation and regeneration in the CNS. Therefore, this review focuses on the current evidence related to the immunomodulatory and neuroregenerative role of cAMP-specific PDE inhibition in the SCI pathophysiology.https://www.mdpi.com/1422-0067/24/9/8135traumatic spinal cord injurycAMPphosphodiesterasesneuroinflammationregeneration |
| spellingShingle | Femke Mussen Jana Van Broeckhoven Niels Hellings Melissa Schepers Tim Vanmierlo Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury International Journal of Molecular Sciences traumatic spinal cord injury cAMP phosphodiesterases neuroinflammation regeneration |
| title | Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury |
| title_full | Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury |
| title_fullStr | Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury |
| title_full_unstemmed | Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury |
| title_short | Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury |
| title_sort | unleashing spinal cord repair the role of camp specific pde inhibition in attenuating neuroinflammation and boosting regeneration after traumatic spinal cord injury |
| topic | traumatic spinal cord injury cAMP phosphodiesterases neuroinflammation regeneration |
| url | https://www.mdpi.com/1422-0067/24/9/8135 |
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