Microtubules have been identified as a powerful target for augmenting regeneration of injured adult axons in the central nervous system. Drugs that stabilize microtubules have shown some promise, but there are concern...Microtubules have been identified as a powerful target for augmenting regeneration of injured adult axons in the central nervous system. Drugs that stabilize microtubules have shown some promise, but there are concerns that abnormally stabilizing microtubules may have only limited benefits for regeneration, while at the same time may be detrimental to the normal work that microtubules perform for the axon. Kinesin-5 （also called kifl I or EgS）, a molecular motor protein best known for its crucial role in mitosis, acts as a brake on microtubule movements by other motor proteins in the axon. Drugs that inhibit kinesin-5, originally developed to treat cancer, result in greater mobility of microtubules in the axon and an overall shift in the forces on the microtubule array. As a result, the axon grows faster, retracts less, and more readily enters environments that are inhibitory to axonal regeneration. Thus, drugs that inhibit kinesin-5 offer a novel microtubule-based means to boost axonal regeneration without the concerns that accompany abnormal stabilization of the microtubule array. Even so, inhibiting kinesin-5 is not without its own caveats, such as potential problems with navigation of the regenerating axon to its target, as well as morphological effects on dendrites that could affect learning and memory if the drugs reach the brain.展开更多
After injury, damaged axons have the capacity to regenerate, but the regenerative capacity of the axon, particularly axons of the central nervous system, is quite limited. This is because the damaged axons tend to ret...After injury, damaged axons have the capacity to regenerate, but the regenerative capacity of the axon, particularly axons of the central nervous system, is quite limited. This is because the damaged axons tend to retract, because they encounter obstacles such as scar tissue and inhibitory molecules, and because their growth rates simply do not match those of a juvenile axon. In recent years, there has been a focus on microtubules as among the most important factors in encouraging injured adult axons to regenerate. Microtubules are hollow polymeric filaments composed of tubulin subunits that provide structural support for the axon.展开更多
基金discussed here on kinesin-5 inhibition as a means for augmenting nerve regeneration after injury was supported mainly by grants from the Craig H.Neilsen Foundation
文摘Microtubules have been identified as a powerful target for augmenting regeneration of injured adult axons in the central nervous system. Drugs that stabilize microtubules have shown some promise, but there are concerns that abnormally stabilizing microtubules may have only limited benefits for regeneration, while at the same time may be detrimental to the normal work that microtubules perform for the axon. Kinesin-5 （also called kifl I or EgS）, a molecular motor protein best known for its crucial role in mitosis, acts as a brake on microtubule movements by other motor proteins in the axon. Drugs that inhibit kinesin-5, originally developed to treat cancer, result in greater mobility of microtubules in the axon and an overall shift in the forces on the microtubule array. As a result, the axon grows faster, retracts less, and more readily enters environments that are inhibitory to axonal regeneration. Thus, drugs that inhibit kinesin-5 offer a novel microtubule-based means to boost axonal regeneration without the concerns that accompany abnormal stabilization of the microtubule array. Even so, inhibiting kinesin-5 is not without its own caveats, such as potential problems with navigation of the regenerating axon to its target, as well as morphological effects on dendrites that could affect learning and memory if the drugs reach the brain.
文摘After injury, damaged axons have the capacity to regenerate, but the regenerative capacity of the axon, particularly axons of the central nervous system, is quite limited. This is because the damaged axons tend to retract, because they encounter obstacles such as scar tissue and inhibitory molecules, and because their growth rates simply do not match those of a juvenile axon. In recent years, there has been a focus on microtubules as among the most important factors in encouraging injured adult axons to regenerate. Microtubules are hollow polymeric filaments composed of tubulin subunits that provide structural support for the axon.
