The role of protein phosphatase 2A tau axis in traumatic brain injury therapy

Abstract

Abstract Background Traumatic brain injury (TBI) is a debilitating disorder due to trauma caused by an external mechanical force eventually leading to disruption in the normal function of the brain, with possible outcomes including permanent or temporary dysfunction of cognitive, physical, and psychosocial abilities. There have been several studies focusing on the search and innovation of neuroprotective agents that could have therapeutic relevance in TBI management. Due to its complexity, TBI is divided into two major components. The first initial event is known as the primary injury; it is a result of the mechanical insult itself and is known to be irreversible and resistant to a vast variety of therapeutics. The secondary event or secondary brain injury is viewed as a cellular injury that does not manifest immediately after the trauma but evolved after a delay period of hours or several days. This category of injury is known to respond favorably to different pharmacological treatment approaches. Main body Due to the complexity in the pathophysiology of the secondary injury, the therapeutic strategy needs to be in a multi-facets model and to have the ability to simultaneously regulate different cellular changes. Several studies have investigated in deep the possible approaches relying on natural compounds as an alternative therapeutic strategy for the management of TBI. In addition, many natural compounds have the potential to target numerous different components of the secondary injury including neuroinflammation, apoptosis, PP2A, tau, and Aβ among others. Here, we review past and current strategies in the therapeutic management of TBI, focusing on the PP2A-tau axis both in animal and human subjects. This review uncovers, in addition, a variety of compounds used in TBI therapy. Conclusion Despite beneficial therapeutic effects observed in animals for many compounds, studies are still needed to be conducted on human subjects to validate their therapeutic virtues. Furthermore, potential therapeutic virtues observed among studies might likely be dependent on the TBI animal model used and the type of induced injury. In addition, specificity and side effects are challenges in TBI therapy specifically which site of PP2A dysfunction to be targeted.

Keywords

• TBI
• PP2A
• Tau