SETDB2-mediated transcriptional repression of IDE in sensory neurons promotes migraine-like pain behaviors in mice - PubMed
5 hours ago
- #SETDB2
- #migraine
- #neuropathic pain
- SETDB2 is a histone methyltransferase significantly upregulated in trigeminal ganglion (TG) neurons in a nitroglycerin-induced chronic migraine mouse model.
- Upregulation of SETDB2 represses the transcription of the insulin-degrading enzyme (IDE) gene by impeding transcription factor KLF4 from binding to the Ide promoter.
- Reduced IDE expression leads to impaired degradation of calcitonin-gene-related peptide (CGRP) in TG neurons, contributing to migraine-like pain behaviors.
- Reversing SETDB2 upregulation reduces H3K9me3 histone marks and alleviates migraine-like pain, while mimicking it induces hypersensitivity.
- Targeting the SETDB2-KLF4-IDE transcriptional axis in sensory neurons may offer therapeutic opportunities for treating migraine.