Work

The Nuclear Translocation of β-catenin in Schwann Cells Influences the Dose-dependent Inhibitory Effects of Flavopiridol on Peripheral Neurodegenerative Processes: A Morpho-pharmacological Approach

Year: 2025

Type: article

Abstract: Background: Flavopiridol (Flavo), a synthetic flavonoid derived from Dysoxylum binectariferum, broadly inhibits cyclin-dependent kinases (CDKs) that regulate transcription in proliferative cells. In the peripheral nervous system, Schwann cells exhibit transcriptional changes during peripheral neurodegenerative processes (PNPs), involving c-Jun and Krox20 as key regulators. Additionally, hydrogen sulfide (H2S) promotes neuroprotection by activating the Wnt/β-catenin pathway, which induces cyclin D1 via β-catenin nuclear translocation. Methods: To assess the therapeutic potential of Flavo in the PNPs, we conducted experiments targeting Schwann cell responses both in vivo and ex vivo. Moreover, we examined changes in transcriptional regulation, focusing on c-Jun and Krox20, and analyzed the effect of Flavo on the H2S/β-catenin/CDK signaling pathway using Western blot and morphological evaluation of demyelination, axonal degeneration, and Schwann cell proliferation. Results: Flavo modulated Schwann cell transcription by shifting the c-Jun/Krox20 balance and significantly suppressed abnormal Schwann cell proliferation. The in vivo analysis revealed that Flavo dose-dependently reduced demyelination and axonal degeneration. Mechanistically, Flavo inhibited the H2S/β-catenin/CDK axis, reducing β-catenin nuclear translocation. Conclusion: Our findings suggest that Flavo provides multifaceted protection in peripheral nerves by correcting transcriptional dysregulation and attenuating key pathological features of Schwann cell dysfunction. Administering Flavo, in relation to the H2S/β-catenin/CDK pathway, may represent a promising therapeutic strategy for peripheral neurodegenerative diseases through multitarget transcriptional modulation.

Source: International Journal of Pharmacology

DOI: 10.31083/ijp45287

Authors: Hyung-Joo Chung, Jimin Lee, Hiroyuki Konishi, Kang-Jae Shin, Na Young Jeong, Junyang Jung

Institutions: Kosin University, Dong-A University, Yamaguchi University, Kyung Hee University

Language: English

Topic: Nerve injury and regeneration

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: National Research Foundation, Kyung Hee University, Ministry of Science, ICT and Future Planning, National Research Foundation of Korea