Molecular targets for axon regeneration: focus on the intrinsic pathways.
Axonal damage and degeneration are prominent components of acute neurological disorders such as stroke, brain and spinal cord injuries, leading to the dysfunction of neuronal networks, which is largely responsible for the impaired neurological function. In the CNS, injured axons not only degenerate but are unable to regenerate and have a limited capacity to sprout and re-establish lost connections. Therefore, axonal damage often results in long term disability. Strategies aimed at fostering neurological recovery by promoting axonal sprouting and regeneration have largely targeted the glial inhibitory environment that develops following central nervous system injury. However, experimental evidence suggests that providing a favorable environment may not be the sole and sufficient means for functional regeneration, and that activating the limited intrinsic potential of neurons to sprout and regenerate may represent an alternative and complementary therapeutic approach. Experimental data that show how the modulation of the intrinsic potential of neurons can promote axonal sprouting and regeneration in the CNS are presented and discussed. These data may suggest future therapeutic opportunities to promote recovery in acute neurological disorders.
Di Giovanni
Simone
S
University of Tuebingen, Center for Neurology, Hertie Institute for Clinical Brain Research, Laboratory for NeuroRegeneration and Repair, Otfried-Mueller Strasse 27, D-72076 Tuebingen, Germany. simone.digiovanni@medizin.uni-tuebingen.de
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology*; D011506:Proteins; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology
D003598:Cytoskeletal Proteins; D046912:Multiprotein Complexes; D009414:Nerve Growth Factors; D011506:Proteins; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases