Axonal Regeneration after Spinal Cord Injury: Molecular Mechanisms, Regulatory Pathways, and Novel Strategies
Mohammed Ibrahim Elmalky,
Gonzalo Alvarez-Bolado,
Alexander Younsi,
Thomas Skutella
Affiliations
Mohammed Ibrahim Elmalky
Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Group for Regeneration and Reprogramming, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany
Gonzalo Alvarez-Bolado
Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Group for Regeneration and Reprogramming, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany
Alexander Younsi
Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
Thomas Skutella
Institute for Anatomy and Cell Biology, Department of Neuroanatomy, Group for Regeneration and Reprogramming, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany
Axonal regeneration in the spinal cord after traumatic injuries presents a challenge for researchers, primarily due to the nature of adult neurons and the inhibitory environment that obstructs neuronal regrowth. Here, we review current knowledge of the intricate network of molecular and cellular mechanisms that hinder axonal regeneration, with a focus on myelin-associated inhibitors (MAIs) and other inhibitory guidance molecules, as well as the pivotal pathways implicated in both inhibiting and facilitating axonal regrowth, such as PKA/AMP, PI3K/Akt/mTOR, and Trk, alongside the regulatory roles of neurotrophins and axonal guidance cues. We also examine current insights into gene therapy, tissue engineering, and pharmacological interventions that show promise in overcoming barriers to axonal regrowth.