Epothilone B and D: Microtubule Stabilization and Axonal Regeneration in Central Nervous System Repair

Abstract: 

The central nervous system (CNS) exhibits limited regenerative capacity following injury, often resulting in permanent neurological deficits. Axon regeneration, essential for functional recovery, is hindered by intrinsic barriers, such as microtubule instability, and extrinsic factors, including glial scarring. Microtubules, dynamic cytoskeletal components, rely on polymerization to support neuronal structure, intracellular transport, and are essential for axonal growth. Microtubules and associated processes are significantly disrupted in the injured CNS, highlighting the need for therapeutic interventions targeting microtubule stabilization. Epothilone B and D are microtubule-stabilizing agents originally developed for oncology that have shown potential in promoting axonal regeneration through enhanced tubulin polymerization and reduced microtubule depolymerization. Additionally, these compounds exhibit neuroprotective properties by mitigating glial scarring and supporting axonal elongation in injury sites. The differential effects of Epothilone B and D on neuronal and non-neuronal cells underscore the need for precise dosing and delivery methods. This review evaluates the mechanisms of action of Epothilone compounds, their synergistic applications with neuroprotective agents such as Gabapentin and Alpha-Lipoic Acid, and their limitations in clinical use. By integrating insights into polymerization dynamics and neuroprotection, this review provides a foundation for advancing CNS repair strategies.