日本名古屋大学一个研究小组日前在《自然—医学》杂志网络版上报告说,治疗头疼的药物“那拉曲坦”可以缓解可引起肌肉萎缩的神经变性疾病的症状。
神经变性疾病是由于蛋白质在神经细胞内外异常蓄积,导致细胞出现障碍并死亡。脊髓延髓肌萎缩症是一种典型的神经变性疾病,只有男性才会发病,其病程呈缓慢、渐进趋势,引起运动神经元的退化性功能紊乱,包括对称性肢体近端肌肉无力、萎缩,吞咽及发音困难等。
研究小组发现,患有脊髓延髓肌萎缩症的实验鼠体内一种名为“CGRP1”的蛋白质出现增加,而让患有脊髓延髓肌萎缩症的实验鼠服用“那拉曲坦”之后,实验鼠的爬行功能和存活期限都得到了改善和延长。如果通过基因操作,使实验鼠体内无法合成这种蛋白质,则患病实验鼠的症状也有所减轻。
研究负责人、名古屋大学教授祖父江元说,此次实验还揭示,如果这种蛋白质异常蓄积,就会导致神经细胞出现障碍。“那拉曲坦”还有望应用于其他神经变性疾病。(生物谷Bioon.com)
doi:10.1038/nm.2932
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Naratriptan mitigates CGRP1-associated motor neuron degeneration caused by an expanded polyglutamine repeat tract
Makoto Minamiyama,Masahisa Katsuno, Hiroaki Adachi, Hideki Doi,Naohide Kondo,Madoka Iida,Shinsuke Ishigaki, Yusuke Fujioka, Shinjiro Matsumoto, Yu Miyazaki,Fumiaki Tanaka,Hiroki Kurihara& Gen Sobue
Spinal and bulbar muscular atrophy (SBMA) is a motor neuron disease caused by the expansion of the CAG triplet repeat within the androgen receptor (AR) gene. Here, we demonstrated that pathogenic AR upregulates the gene encoding calcitonin gene-related peptide α (CGRP1). In neuronal cells, overexpression of CGRP1 induced cellular damage via the activation of the c-Jun N-terminal kinase (JNK) pathway, whereas pharmacological suppression of CGRP1 or JNK attenuated the neurotoxic effects of pathogenic AR. The depletion of CGRP1 inactivated JNK and suppressed neurodegeneration in a mouse model of SBMA. Naratriptan, a serotonin 1B/1D (5-hydroxytryptamine 1B/1D, or 5-HT1B/1D) receptor agonist, decreased CGRP1 expression via the induction of dual-specificity protein phosphatase 1 (DUSP1), attenuated JNK activity and mitigated pathogenic AR-mediated neuronal damage in cellular and mouse SBMA models. These observations suggest that pharmacological activation of the 5-HT1B/1D receptor may be used therapeutically to treat SBMA and other polyglutamine-related neurodegenerative diseases.