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The anatomical structure of the mammalian cerebral cortex is the essential foundation for its complex neural activity. This structure is developed by proliferation, differentiation, and migration of neural progenitor cells (NPCs), the fate of which is spatially and temporally regulated by the proper gene. This study was used in utero electroporation and found that the well‐known oncogene c‐Myc mainly promoted NPCs' proliferation and their transformation into intermediate precursor cells. Furthermore, the obtained results also showed that c‐Myc blocked the differentiation of NPCs to postmitotic neurons, and the expression of telomere reverse transcriptase was controlled by c‐Myc in the neocortex. These findings indicated c‐Myc as a key regulator of the fate of NPCs during the development of the cerebral cortex. [ABSTRACT FROM AUTHOR]

While axon regeneration is a key determinant of functional recovery of the nervous system after injury, it is often poor in the mature nervous system. Influx of extracellular calcium (Ca2+) is one of the first phenomena that occur following axonal injury, and calcium/calmodulin‐dependent protein kinase II (CaMKII), a target substrate for calcium ions, regulates the status of cytoskeletal proteins such as F‐actin. Herein, we found that peripheral axotomy activates CaMKII in dorsal root ganglion (DRG) sensory neurons, and inhibition of CaMKII impairs axon outgrowth in both the peripheral and central nervous systems (PNS and CNS, respectively). Most importantly, we also found that the activation of CaMKII promotes PNS and CNS axon growth, and regulatory effects of CaMKII on axon growth occur via affecting the length of the F‐actin. Thus, we believe our findings provide clear evidence that CaMKII is a critical modulator of mammalian axon regeneration. [ABSTRACT FROM AUTHOR]

The inflammatory response is a critical regulator for the regeneration of axon following nervous system injury. Nuclear factor‐kappa B (NF‐κB) is characteristically known for its ubiquitous role in the inflammatory response. However, its functional role in adult mammalian axon growth remains elusive. Here, we found that the NF‐κB signaling pathway is activated in adult sensory neurons through peripheral axotomy. Furthermore, inhibition of NF‐κB in peripheral sensory neurons attenuated their axon growth in vitro and in vivo. Our results also showed that NF‐κB modulated axon growth by repressing the phosphorylation of STAT3. Furthermore, activation of STAT3 significantly promoted adult optic nerve regeneration. Taken together, the findings of our study indicated that NF‐κB/STAT3 cascade is a critical regulator of intrinsic axon growth capability in the adult nervous system. [ABSTRACT FROM AUTHOR]

Objective: In this study, we used a bibliometric and visual analysis to evaluate the characteristics of the 100 most cited articles on axon regeneration., Methods: The 100 most cited papers on axon regeneration published between 2003 and 2023 were identified by searching the Web of Science Core Collection database. The extracted data included the title, author, keywords, journal, publication year, country, and institution. A bibliometric analysis was subsequently undertaken., Results: The examined set of 100 papers collectively accumulated a total of 39,548 citations. The number of citations for each of the top 100 articles ranged from 215 to 1,604, with a median value of 326. The author with the most contributions to this collection was He, Zhigang, having authored eight papers. Most articles originated in the United States ( n  = 72), while Harvard University was the institution with the most cited manuscripts ( n  = 19). Keyword analysis unveiled several research hotspots, such as chondroitin sulfate proteoglycan, alternative activation, exosome, Schwann cells, axonal protein synthesis, electrical stimulation, therapeutic factors, and remyelination. Examination of keywords in the articles indicated that the most recent prominent keyword was "local delivery.", Conclusion: This study offers bibliometric insights into axon regeneration, underscoring that the United States is a prominent leader in this field. Our analysis highlights the growing relevance of local delivery systems in axon regeneration. Although these systems have shown promise in preclinical models, challenges associated with long-term optimization, agent selection, and clinical translation remain. Nevertheless, the continued development of local delivery technologies represents a promising pathway for achieving axon regeneration; however, additional research is essential to fully realize their potential and thereby enhance patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Saijilafu, Ye, Zhang and Xu.)

Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration. SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration., (Copyright © 2019 the authors.)