GSK-3β: An exuberating neuroinflammatory mediator in Parkinson's disease

Neuroinflammation is a critical degradative condition affecting neurons in the brain. Progressive neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease (PD) have been strongly linked to neuroinflammation. The trigger point for inflammatory conditions in the cells and body is the physiological immune system. The immune response mediated by glial cells and astrocytes can rectify the physiological alterations occurring in the cell for the time being but prolonged activation leads to pathological progression. The proteins mediating such an inflammatory response, as per the available literature, are undoubtedly GSK-3β, NLRP3, TNF, PPARγ, and NF-κB, along with a few other mediatory proteins. NLRP3 inflammasome is undeniably a principal instigator of the neuroinflammatory response, but the regulatory pathways controlling its activation are still unclear, besides less clarity for the interplay between different inflammatory proteins. Recent reports have suggested the involvement of GSK-3β in regulating NLRP3 activation, but the exact mechanistic pathway remains vague. In the current review, we attempt to provide an elaborate description of crosstalk between inflammatory markers and GSK-3β mediated neuroinflammation progression, linking it to regulatory transcription factors and posttranslational modification of proteins. The recent clinical therapeutic advances targeting these proteins are also discussed in parallel to provide a comprehensive view of the progress made in PD management and lacunas still existing in the field.