Developing strategies for enhancing axon regeneration through modifications of the microtubules
Funded in: 2013, 2014, 2015
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Problem: Axonal injury hinders the regrowth of the axon by disassembling the microtubules
Target: Microtubules of the neuron, the “skeleton” of the cell
Goal: promote microtubules elongation to induce regeneration
The regeneration of the injured axons after spinal cord injury depends on several mechanisms. There are for example scar building, inhibitors of the regrowth released by the injured tissue fragments and the ability of the inured axons to regenerate that is regulated by intracellular growth stimulating pathways. Initiating of axon regrowth involves the regeneration of a severed axon stump into a motile growth cone.
The injury of the axons damages the structures of the cytoskeleton. Microtubules are components of the cytoskeleton, which consist of polarized, dynamic protein filaments. Microtubules are part of a structural network and take part in a variety of cellular processes. The primary role of the microtubule cytoskeleton is the structural support, but they are as well involved in the intracellular transport, in cell division and also in regeneration by building a motile growth cone. After axonal injury the microtubules disassemble hindering the regrowth of the axon. Regeneration of the axon requires a motile growth cone involving the reorganization of the microtubules and coordinated regulation of their dynamic polarization.
Frank Bradke’s team focuses on the intracellular mechanisms regulating axon growth during the development and after injury with a particular emphasis onto cytoskeleton. Their results indicate that the intracellular mechanisms mediating axon growth during development share similarities with the ones that could regulate axon regeneration. Recently published work has shown that a moderate dose of Taxol, an already clinical used chemotherapeutic agent, can dramatically enhance axon regrowth. This biological effect of Taxol is exerted by a moderate stabilization of the axonal microtubules.
This project has the goal to decipher the molecular players that regulate the dynamic generation and stabilization of the microtubules. The aim is to find an effective strategy to promote the regeneration of axons by targeting the regulation of microtubules.