Nicoletti Vincenzo Giuseppe, Pajer Krisztián, Calcagno Damiano, Pajenda Gholam, Nógrádi Antal
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section of Medical Biochemistry, University of Catania, 95124 Catania, Italy.
Department of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, 6720 Szeged, Hungary.
Biomolecules. 2022 Jul 22;12(8):1015. doi: 10.3390/biom12081015.
Mature neurotrophic factors and their propeptides play key roles ranging from the regulation of neuronal growth and differentiation to prominent participation in neuronal survival and recovery after injury. Their signaling pathways sculpture neuronal circuits during brain development and regulate adaptive neuroplasticity. In addition, neurotrophic factors provide trophic support for damaged neurons, giving them a greater capacity to survive and maintain their potential to regenerate their axons. Therefore, the modulation of these factors can be a valuable target for treating or preventing neurologic disorders and age-dependent cognitive decline. Neuroregenerative medicine can take great advantage by the deepening of our knowledge on the molecular mechanisms underlying the properties of neurotrophic factors. It is indeed an intriguing topic that a significant interplay between neurotrophic factors and various metals can modulate the outcome of neuronal recovery. This review is particularly focused on the roles of GDNF, BDNF and NGF in motoneuron survival and recovery from injuries and evaluates the therapeutic potential of various neurotrophic factors in neuronal regeneration. The key role of metal homeostasis/dyshomeostasis and metal interaction with neurotrophic factors on neuronal pathophysiology is also highlighted as a novel mechanism and potential target for neuronal recovery. The progress in mechanistic studies in the field of neurotrophic factor-mediated neuroprotection and neural regeneration, aiming at a complete understanding of integrated pathways, offers possibilities for the development of novel neuroregenerative therapeutic approaches.
成熟的神经营养因子及其前体肽发挥着关键作用，范围从调节神经元的生长和分化到在损伤后显著参与神经元的存活和恢复。它们的信号通路在大脑发育过程中塑造神经元回路，并调节适应性神经可塑性。此外，神经营养因子为受损神经元提供营养支持，使其有更大的存活能力并维持其轴突再生的潜力。因此，调节这些因子可能是治疗或预防神经系统疾病和年龄依赖性认知衰退的一个有价值的靶点。神经再生医学可以通过加深我们对神经营养因子特性背后分子机制的了解而受益匪浅。神经营养因子与各种金属之间的显著相互作用能够调节神经元恢复的结果，这确实是一个引人入胜的话题。本综述特别关注胶质细胞源性神经营养因子（GDNF）、脑源性神经营养因子（BDNF）和神经生长因子（NGF）在运动神经元存活和损伤恢复中的作用，并评估各种神经营养因子在神经元再生中的治疗潜力。金属稳态/失衡以及金属与神经营养因子的相互作用对神经元病理生理学的关键作用也被强调为神经元恢复的一种新机制和潜在靶点。神经营养因子介导的神经保护和神经再生领域的机制研究进展，旨在全面理解整合通路，为开发新的神经再生治疗方法提供了可能性。
