日本名古屋大學一個研究小組日前在《自然—醫(yī)學》雜志網(wǎng)絡版上報告說,，治療頭疼的藥物“那拉曲坦”可以緩解可引起肌肉萎縮的神經(jīng)變性疾病的癥狀。
神經(jīng)變性疾病是由于蛋白質(zhì)在神經(jīng)細胞內(nèi)外異常蓄積,，導致細胞出現(xiàn)障礙并死亡,。脊髓延髓肌萎縮癥是一種典型的神經(jīng)變性疾病,，只有男性才會發(fā)病，其病程呈緩慢,、漸進趨勢,，引起運動神經(jīng)元的退化性功能紊亂，包括對稱性肢體近端肌肉無力,、萎縮,，吞咽及發(fā)音困難等。
研究小組發(fā)現(xiàn),，患有脊髓延髓肌萎縮癥的實驗鼠體內(nèi)一種名為“CGRP1”的蛋白質(zhì)出現(xiàn)增加,，而讓患有脊髓延髓肌萎縮癥的實驗鼠服用“那拉曲坦”之后，實驗鼠的爬行功能和存活期限都得到了改善和延長,。如果通過基因操作,，使實驗鼠體內(nèi)無法合成這種蛋白質(zhì)，則患病實驗鼠的癥狀也有所減輕,。
研究負責人,、名古屋大學教授祖父江元說，此次實驗還揭示,，如果這種蛋白質(zhì)異常蓄積,，就會導致神經(jīng)細胞出現(xiàn)障礙。“那拉曲坦”還有望應用于其他神經(jīng)變性疾病,。（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.
