ArticleGlia2021
Mek/ERK1/2-MAPK and PI3K/Akt/mTOR signaling plays both independent and cooperative roles in Schwann cell differentiation, myelination and dysmyelination.
Article in Glia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Gamma-oryzanol promotes neurite extension in NGF-primed PC12 cells and enhances viability/process elongation in immortalized Schwann cells.The journal of physiological sciences : JPS · 2026Article
- Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain.Neural regeneration research · 2026Article
- Hypoxia-preconditioned mitochondrial transplantation multidirectionally modulates Schwann cell functions to repair peripheral nerve injury in rats.Journal of orthopaedic translation · 2026Article
- LARP7 enhances the potential of dental pulp stem cells to promote peripheral nerve repair.Stem cells (Dayton, Ohio) · 2026Article
- Longitudinal analysis of lipid changes in the sciatic nerve caused by overexpression of PMP22 in murine models of CMT1A.Journal of lipid research · 2026Article
- Extracorporeal Shock Wave Therapy Promotes Peripheral Nerve Regeneration Through ERK1/2-Mediated Autophagy.Annals of the New York Academy of Sciences · 2026Article
- Schwann Cell Synthesized Cholesterol Orchestrates Peripheral Nerve Regeneration via Structural and IGF1-Dependent Signaling Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Repetitive transcranial magnetic stimulation suppresses glia-associated neuroinflammation and promotes peripheral nerve recovery in neuropathic pain.Frontiers in immunology · 2026Article
- Plasticity, injury-induced reprogramming, and translational applications of Schwann cells in neural regeneration.Frontiers in cellular neuroscience · 2026Review
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- New insights into the influence of temperature on axonal transport and function in myelinated regions of Schwann cells.iScience · 2025Review
- Thermal Annealing Enhances Piezoelectricity and Regenerative Potential of PVDF-TrFE Nanofiber Scaffolds.Advanced materials technologies · 2025Article
- NetREm: Network Regression Embeddings reveal cell-type transcription factor coordination for gene regulation.Bioinformatics advances · 2025Article
- Mechanosensitive Piezo1 channel: an emerging target in demyelination disease.Frontiers in cellular neuroscience · 2025Review
- Roles of ERK signaling pathway in regulating myelination of the peripheral nervous system.Frontiers in molecular neuroscience · 2025Review
- Role and Interplay of Different Signaling Pathways Involved in Sciatic Nerve Regeneration.Journal of molecular neuroscience : MN · 2024Review
- Homosalate and ERK Knockdown in the Modulation ofCurrent issues in molecular biology · 2024Article
- Neuritin accelerates Schwann cell dedifferentiation via PI3K/Akt/mTOR signalling pathway during Wallerian degeneration.Journal of cellular and molecular medicine · 2024Article
- Effects of Physical Cues on Stem Cell-Derived Extracellular Vesicles toward Neuropathy Applications.Biomedicines · 2024Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Multiple signals are involved in the regulation of developmental myelination by Schwann cells and in the maintenance of a normal myelin homeostasis throughout adult life, preserving the integrity of the axons in the PNS. Recent studies suggest that Mek/ERK1/2-MAPK and PI3K/Akt/mTOR intracellular signaling pathways play important, often overlapping roles in the regulation of myelination in the PNS. In addition, hyperactivation of these signaling pathways in Schwann cells leads to a late onset of various pathological changes in the sciatic nerves. However, it remains poorly understood whether these pathways function independently or sequentially or converge using a common mechanism to facilitate Schwann cell differentiation and myelin growth during development and in causing pathological changes in the adult animals. To address these questions, we analyzed multiple genetically modified mice using simultaneous loss- and constitutive gain-of-function approaches. We found that during development, the Mek/ERK1/2-MAPK pathway plays a primary role in Schwann cell differentiation, distinct from mTOR. However, during active myelination, ERK1/2 is dependent on mTOR signaling to drive the growth of the myelin sheath and regulate its thickness. Finally, our data suggest that peripheral nerve pathology during adulthood caused by hyperactivation of Mek/ERK1/2-MAPK or PI3K is likely to be independent or dependent on mTOR-signaling in different contexts. Thus, this study highlights the complexities in the roles played by two major intracellular signaling pathways in Schwann cells that affect their differentiation, myelination, and later PNS pathology and predicts that potential therapeutic modulation of these pathways in PNS neuropathies could be a complex process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.