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Cell Pathways Underlying Neuronal Differentiation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 2321

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Guest Editor
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
Interests: neurodegeneration; spinal cord; motor neurons; glioblastoma; autophagy; light microscopy
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Special Issue Information

Dear Colleagues,

Cell differentiation in mammals represents a critical process during which totipotent or pluripotent cells progressively acquire morphological and biochemical features of specific mature phenotypes. This process mainly occurs during embryonic development, while it drastically reduces in adult life. This is especially true for neurons. In fact, although the persistence of neurogenic niches in adult life has been demonstrated and adult neurogenesis has been described in experimental models, the occurrence of neurogenesis in humans still remains controversial, and the generation of new neurons in an adult organism represents a challenging new frontier for regenerative medicine. In recent years, advances in methodological and technological procedures have allowed new treatments to be developed, capable of inducing stem-like neural progenitor cells and even somatic cells to reprogram their differentiation in fate and convert them into neurons.

The present Special Issue aims to collect the more recent research data obtained in experimental models both in vivo and in vitro, which provide new insights regarding the molecular mechanisms and cell pathways that are key to directing undifferentiated, stem-like neural cells toward a neuronal phenotype. These findings, apart from being essential to increasing our knowledge of neurobiology, might contribute to the development of new therapeutic strategies in order to counteract several human neuronal pathologies such as brain and spinal cord injury and brain tumors.

Dr. Michela Ferrucci
Guest Editor

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Keywords

  • neural progenitor cells
  • neuronal cell lines
  • induced pluripotent stem cells
  • neuronal phenotype
  • brain tumor cells

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Published Papers (2 papers)

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Research

34 pages, 11954 KiB  
Article
Retinoic Acid Promotes Neuronal Differentiation While Increasing Proteins and Organelles Related to Autophagy
by Gloria Lazzeri, Paola Lenzi, Giulia Signorini, Sara Raffaelli, Elisa Giammattei, Gianfranco Natale, Riccardo Ruffoli, Francesco Fornai and Michela Ferrucci
Int. J. Mol. Sci. 2025, 26(4), 1691; https://doi.org/10.3390/ijms26041691 - 16 Feb 2025
Viewed by 846
Abstract
Retinoic acid (RA) is commonly used to differentiate SH-SY5Y neuroblastoma cells. This effect is sustained by a specific modulation of gene transcription, leading to marked changes in cellular proteins. In this scenario, autophagy may be pivotal in balancing protein synthesis and degradation. The [...] Read more.
Retinoic acid (RA) is commonly used to differentiate SH-SY5Y neuroblastoma cells. This effect is sustained by a specific modulation of gene transcription, leading to marked changes in cellular proteins. In this scenario, autophagy may be pivotal in balancing protein synthesis and degradation. The present study analyzes whether some autophagy-related proteins and organelles are modified during RA-induced differentiation of SH-SY5Y cells. RA-induced effects were compared to those induced by starvation. SH-SY5Y cells were treated with a single dose of 10 µM RA or grown in starvation, for 3 days or 7 days. After treatments, cells were analyzed at light microscopy and transmission electron microscopy to assess cell morphology and immunostaining for specific markers (nestin, βIII-tubulin, NeuN) and some autophagy-related proteins (Beclin 1, LC3). We found that both RA and starvation differentiate SH-SY5Y cells. Specifically, cell differentiation was concomitant with an increase in autophagy proteins and autophagy-related organelles. However, the effects of a single dose of 10 μM RA persist for at least 7 days, while prolonged starvation produces cell degeneration and cell loss. Remarkably, the effects of RA are modulated in the presence of autophagy inhibitors or stimulators. The present data indicate that RA-induced differentiation is concomitant with an increased autophagy. Full article
(This article belongs to the Special Issue Cell Pathways Underlying Neuronal Differentiation)
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14 pages, 3388 KiB  
Article
Impact of Larval Sertraline Exposure on Alternative Splicing in Neural Tissue of Adult Drosophila melanogaster
by Luis Felipe Santos-Cruz, Myriam Campos-Aguilar, Laura Castañeda-Partida, Santiago Cristobal Sigrist-Flores, María Eugenia Heres-Pulido, Irma Elena Dueñas-García, Elías Piedra-Ibarra, Rafael Jiménez-Flores and Alberto Ponciano-Gómez
Int. J. Mol. Sci. 2025, 26(2), 563; https://doi.org/10.3390/ijms26020563 - 10 Jan 2025
Viewed by 1067
Abstract
Sertraline, a selective serotonin reuptake inhibitor (SSRI), is commonly used to treat various psychiatric disorders such as depression and anxiety due to its ability to increase serotonin availability in the brain. Recent findings suggest that sertraline may also influence the expression of genes [...] Read more.
Sertraline, a selective serotonin reuptake inhibitor (SSRI), is commonly used to treat various psychiatric disorders such as depression and anxiety due to its ability to increase serotonin availability in the brain. Recent findings suggest that sertraline may also influence the expression of genes related to synaptic plasticity and neuronal signaling pathways. Alternative splicing, a process that allows a single gene to produce multiple protein isoforms, plays a crucial role in the regulation of neuronal functions and plasticity. Dysregulation of alternative splicing events has been linked to various neurodevelopmental and neurodegenerative diseases. This study aims to explore the effects of sertraline on alternative splicing events, including exon inclusion, exon exclusion, and mutually exclusive splicing events, in genes associated with neuronal function in Drosophila melanogaster and to use this model to investigate the molecular impacts of SSRIs on gene regulation in the nervous system. RNA sequencing (RNA-seq) was performed on central nervous system samples from Drosophila melanogaster adults exposed to sertraline for 24 h when they were third instar larvae. Alternative splicing events were analyzed to identify changes in exon inclusion and exclusion, as well as intron retention. Sertraline treatment significantly altered alternative splicing patterns in key genes related to neuronal stability and function. Specifically, sertraline promoted the inclusion of long Ank2 isoforms, suggesting enhanced axonal stability, and favored long ATPalpha isoforms, which support Na+/K+ ATPase activity essential for ionic balance and neuronal excitability. Intron retention in the yuri gene suggests that cytoskeletal reorganization could impact neuronal morphology. Additionally, splicing alterations in sxc and Atg18a indicate a potential influence of sertraline on epigenetic regulation and autophagy processes, fundamental aspects for neuronal plasticity and cellular homeostasis. These findings suggest that sertraline influences alternative splicing in the central nervous system of Drosophila melanogaster, potentially contributing to its therapeutic effects by modulating neuronal stability and adaptability. Full article
(This article belongs to the Special Issue Cell Pathways Underlying Neuronal Differentiation)
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