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ROCK inhibition promotes axon and myelin regeneration via PI3K/Akt/GSK3β in a mouse sciatic nerve injury model

Year: 2025

Type: article

Abstract: . Additionally, RSC96 Schwann cell migration and proliferation were evaluated using scratch assays and EdU staining. Results showed that ROCK inhibition with Y27632 significantly enhanced axonal regeneration, growth cone expansion, retrograde transport, and reinnervation of acetylcholine receptors and Merkel cells, and promoted Schwann cell proliferation and RSC96 migration, leading to thicker myelin sheaths after SNC. These changes mitigated gastrocnemius muscle atrophy, improved muscle strength, gait, and thermal/tactile sensitivity. Co‑treatment with LY294002 blocked these effects, but adding SB216763 restored them. Protein analysis indicated that ROCK inhibition increased phosphorylated PI3K, Akt and GSK3β, whereas PI3K inhibition reduced GSK3β phosphorylation. These findings suggested that ROCK inhibition promotes axon regeneration and remyelination after PNI by enhancing PI3K/Akt phosphorylation and suppressing GSK3β activity, highlighting the therapeutic potential of targeting the ROCK/PI3K/Akt/GSK3β pathway for peripheral nerve repair.

Source: International Journal of Molecular Medicine

DOI: 10.3892/ijmm.2025.5685

Authors: Shuang Dou, Zhijun Li, Boyao Zheng, Zhenyu Ren, Hai Wang, Qing Zuo, Fang Fang, Yuehong Zhuang

Institutions: Fujian Medical University, First Affiliated Hospital of Fujian Medical 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

OpenAlex ID: W4415909182

FWCI:

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