Department of Developmental Neurology and Epileptology, Polish Mother's Memorial Hospital Research Institute, 93-338 Lodz, Poland.
Department of Gynaecology and Obstetrics, Medical University of Lodz, 93-338 Lodz, Poland.
Int J Mol Sci. 2022 May 30;23(11):6151. doi: 10.3390/ijms23116151.
The calcitonin gene-related peptide (CGRP) is implicated in the pathogenesis of several pain-related syndromes, including migraine. Targeting CGRP and its receptor by their antagonists and antibodies was a breakthrough in migraine therapy, but the need to improve efficacy and limit the side effects of these drugs justify further studies on the regulation of CGRP in migraine. The expression of the CGRP encoding gene, , is modulated by epigenetic modifications, including the DNA methylation, histone modification, and effects of micro RNAs (miRNAs), circular RNAs, and long-coding RNAs (lncRNAs). On the other hand, CGRP can change the epigenetic profile of neuronal and glial cells. The promoter of the gene has two CpG islands that may be specifically methylated in migraine patients. DNA methylation and lncRNAs were shown to play a role in the cell-specific alternative splicing of the primary transcript. CGRP may be involved in changes in neural cytoarchitecture that are controlled by histone deacetylase 6 (HDAC6) and can be related to migraine. Inhibition of HDAC6 results in reduced cortical-spreading depression and a blockade of the CGRP receptor. CGRP levels are associated with the expression of several miRNAs in plasma, making them useful peripheral markers of migraine. The fundamental role of CGRP in inflammatory pain transmission may be epigenetically regulated. In conclusion, epigenetic connections of CGRP should be further explored for efficient and safe antimigraine therapy.
降钙素基因相关肽（CGRP）与多种疼痛相关综合征的发病机制有关，包括偏头痛。通过其拮抗剂和抗体靶向 CGRP 和其受体是偏头痛治疗的突破，但需要提高疗效并限制这些药物的副作用，这证明进一步研究偏头痛中 CGRP 的调节是合理的。CGRP 编码基因 的表达受表观遗传修饰的调节，包括 DNA 甲基化、组蛋白修饰以及 microRNAs（miRNAs）、环状 RNA 和长编码 RNA（lncRNAs）的作用。另一方面，CGRP 可以改变神经元和神经胶质细胞的表观遗传特征。 基因的启动子有两个 CpG 岛，在偏头痛患者中可能会被特异性甲基化。研究表明，DNA 甲基化和 lncRNAs 参与了 基因的初级转录物的细胞特异性选择性剪接。CGRP 可能参与由组蛋白去乙酰化酶 6（HDAC6）控制的神经细胞结构变化，并且可能与偏头痛有关。抑制 HDAC6 会导致皮质扩散性抑制减少，并阻断 CGRP 受体。CGRP 水平与血浆中几种 miRNA 的表达相关，使它们成为偏头痛的有用外周标志物。CGRP 在炎症性疼痛传递中的基本作用可能受到表观遗传调控。总之，应进一步探索 CGRP 的表观遗传联系，以实现有效和安全的抗偏头痛治疗。
