ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2024
Targeting the Hippo pathway in Schwann cells ameliorates peripheral nerve degeneration via a polypharmacological mechanism.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Distinct Role of Specialized Cutaneous Schwann Cell Network in Acute and Chronic Pain Sensation.Neuroscience bulletin · 2026Article
- M2 polarization of macrophage induced by IL-33 promotes mouse sciatic nerve regeneration.Cell & bioscience · 2026Article
- Detection of MicroRNAs Released from Argonautes.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Phosphorylation of an RNA-Binding Protein Rck/Me31b by Hippo Is Essential for Adipose Tissue Aging.Aging cell · 2025Article
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20 authors.
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Abstract
Peripheral neuropathies (PNs) are common diseases in elderly individuals characterized by Schwann cell (SC) dysfunction and irreversible Wallerian degeneration (WD). Although the molecular mechanisms of PN onset and progression have been widely studied, therapeutic opportunities remain limited. In this study, we investigated the pharmacological inhibition of Mammalian Ste20-like kinase 1/2 (MST1/2) by using its chemical inhibitor, XMU-MP-1 (XMU), against WD. XMU treatment suppressed the proliferation, dedifferentiation, and demyelination of SCs in models of WD in vitro, in vivo, and ex vivo. As a downstream mediator of canonical and noncanonical Hippo/MST1 pathway activation, the mature microRNA (miRNA) let-7b and its binding partners quaking homolog (QKI)/nucleolin (NCL) modulated miRNA-mediated silencing of genes involved in protein transport. Hence, direct phosphorylation of QKI and NCL by MST1 might be critical for WD onset and pathogenesis. Moreover, p38α/mitogen-activated protein kinase 14 (p38α) showed a strong affinity for XMU, and therefore, it may be an alternative XMU target for controlling WD in SCs. Taken together, our findings provide new insights into the Hippo/MST pathway function in PNs and suggest that XMU is a novel multitargeted therapeutic for elderly individuals with PNs.
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