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The study investigates the role of the endoplasmic reticulum (ER) stress response pathway in the development of plexiform neurofibromas (PNFs) in patients with neurofibromatosis type 1 (NF1). The researchers found that all three UPR pathways were activated in PNFs and the protein kinase RNA (PKR)-like ER kinase (PERK) was the most highly expressed. The study suggests that inhibiting PERK could reduce the number of neurofibroma cells and the size of PNFs in mouse models. The loss of Nf1 was found to activate PERK-eIF2α-ATF4 signaling, which led to an increase in protein synthesis and tumor formation. The study proposes that targeting protein stability could provide a novel therapeutic approach for PNFs.
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