Modulation of the LIMK Pathway by Myricetin: A Protective Strategy Against Neurological Impairments in Spinal Cord Injury
- Author:
Abhishek ROY
1
;
Santimoy SEN
;
Rudradip DAS
;
Amit SHARD
;
Hemant KUMAR
Author Information
- Publication Type:Original Article
- From: Neurospine 2024;21(3):878-889
- CountryRepublic of Korea
- Language:English
-
Abstract:
Objective:Spinal cord injury (SCI), one of the major disabilities concerning central nervous system injury, results in permanent tissue loss and neurological impairment. The existing therapeutic options for SCI are limited and predominantly consist of chemical compounds. In this study, we delved into the neuroprotective effects of myricetin, a natural flavonoid compound, and the underlying mechanisms, specifically in the context of SCI, utilizing an in vivo model. Previously, our investigations revealed an elevation in the phosphorylated form of Lin-11, Isl-1, and Mec-3 kinase1 (LIMK1) at chronic time points postinjury, coinciding with neuronal loss and scar formation. Our primary objective here was to assess the potential neuroprotective properties of myricetin in SCI and to ascertain if these effects were linked to LIMK inhibition, a hitherto unexamined pathway to date.
Methods:Computational docking and molecular dynamics simulation studies were performed to assess myricetin’s potential to bind with LIMK. Then, using a rat contusion model, SCI was induced and different molecular techniques (Western blot, Evans Blue assay, quantitative reverse transcription polymerase chain reaction and immunohistochemistry) were performed to determine the effects of myricetin.
Results:Remarkably, computational docking models identified myricetin as having a better interaction profile with LIMK than standard. Subsequent to myricetin treatment, a significant downregulation in phosphorylated LIMK expression was observed at chronic time points. This reduction correlated with a notable decrease in glial and fibrotic scar formation, and enhanced neuroprotection indicating a positive outcome in vivo.
Conclusion:In summary, our findings underscore myricetin’s potential as a bioactive compound capable of attenuating SCI-induced injury cascades by targeting the LIMK pathway.
