Abstract

Microtubules (MTs) are highly dynamic polymers essential for a wide range of cellular physiologies, such as acting as directional railways for intracellular transport and position, guiding chromosome segregation during cell division, and controlling cell polarity and morphogenesis. Evidence has established that maintaining microtubule (MT) stability in neurons is vital for fundamental cellular and developmental processes, such as neurodevelopment, degeneration, and regeneration. To fulfill these diverse functions, the nervous system employs an arsenal of microtubule-associated proteins (MAPs) to control MT organization and function. Subsequent studies have identified that the disruption of MT function in neurons is one of the most prevalent and important pathological features of traumatic nerve damage and neurodegenerative diseases and that this disruption manifests as a reduction in MT polymerization and concomitant deregulation of the MT cytoskeleton, as well as downregulation of microtubule-associated protein (MAP) expression. A variety of MT-targeting agents that reverse this pathological condition, which is regarded as a therapeutic opportunity to intervene the onset and development of these nervous system abnormalities, is currently under development. Here, we provide an overview of the MT-intrinsic organization process and how MAPs interact with the MT cytoskeleton to promote MT polymerization, stabilization, and bundling. We also highlight recent advances in MT-targeting therapeutic agents applied to various neurological disorders. Together, these findings increase our current understanding of the function and regulation of MT organization in nerve growth and regeneration.

Highlights

  • A multitude of cellular processes rely on the cytoskeleton, a filamentous scaffold of proteins that is essential for cell morphogenesis and division and intracellular transport

  • We discuss the current state of microtubule-stabilizing agents (MSAs), a new pharmacological intervention for treating central nervous system disorders, and address several microtubuledestabilizing agents (MDAs) as therapeutic strategies for suppressing cancer activity and vasculogenesis. Such diversified MT functions may provide us with new insights into MT-targeting therapies that mitigate structural and functional alterations linked to nervous system disorders

  • Injury to the central nervous system (CNS) induces severe neurological complications for individuals with traumatic brain injury (TBI) or spinal cord injury (SCI) because various inhibitory factors secreted by oligodendrocytes and scar-forming cells and the poor intrinsic growth ability upon neuronal maturation hamper axon regeneration and functional recovery [86, 87]

Read more

Summary

Introduction

A multitude of cellular processes rely on the cytoskeleton, a filamentous scaffold of proteins that is essential for cell morphogenesis and division and intracellular transport. Oxidative Medicine and Cellular Longevity and have a nearly uniform polarity orientation [5] This oriented array allows the directional transport of cargoes to be properly orchestrated. We discuss the current state of microtubule-stabilizing agents (MSAs), a new pharmacological intervention for treating central nervous system disorders, and address several microtubuledestabilizing agents (MDAs) as therapeutic strategies for suppressing cancer activity and vasculogenesis. Such diversified MT functions may provide us with new insights into MT-targeting therapies that mitigate structural and functional alterations linked to nervous system disorders

MT Organization and Dynamic Regulation in Eukaryotic Cells
Types of MT Regulatory Proteins
MT Organization in Neurons
MT Modifications in Nervous System Injury
MT-Targeting Agent
Concluding Remarks and Future Perspectives
Conflicts of Interest
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call