The Struggle to Make CNS Axons Regenerate: Why Has It Been so Difficult?

0540367 - ÚEM 2021 RIV US eng J - Článek v odborném periodiku
Fawcett, James
The Struggle to Make CNS Axons Regenerate: Why Has It Been so Difficult?
Neurochemical Research. Roč. 45, č. 1 (2020), s. 144-158. ISSN 0364-3190. E-ISSN 1573-6903
Grant CEP: GA MŠMT(CZ) EF15_003/0000419
Institucionální podpora: RVO:68378041
Klíčová slova: axon regeneration * chondroitin sulphate proteoglycans * NogoA
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 3.996, rok: 2020
Způsob publikování: Open access
https://link.springer.com/article/10.1007/s11064-019-02844-y

Axon regeneration in the CNS is inhibited by many extrinsic and intrinsic factors. Because these act in parallel, no single intervention has been sufficient to enable full regeneration of damaged axons in the adult mammalian CNS. In the external environment, NogoA and CSPGs are strongly inhibitory to the regeneration of adult axons. CNS neurons lose intrinsic regenerative ability as they mature: embryonic but not mature neurons can grow axons for long distances when transplanted into the adult CNS, and regeneration fails with maturity in in vitro axotomy models. The causes of this loss of regeneration include partitioning of neurons into axonal and dendritic fields with many growth-related molecules directed specifically to dendrites and excluded from axons, changes in axonal signalling due to changes in expression and localization of receptors and their ligands, changes in local translation of proteins in axons, and changes in cytoskeletal dynamics after injury. Also with neuronal maturation come epigenetic changes in neurons, with many of the transcription factor binding sites that drive axon growth-related genes becoming inaccessible. The overall aim for successful regeneration is to ensure that the right molecules are expressed after axotomy and to arrange for them to be transported to the right place in the neuron, including the damaged axon tip.
Trvalý link: http://hdl.handle.net/11104/0317999