通過改造一種導(dǎo)致肉毒中毒的神經(jīng)毒素的基本組成部分,，科學(xué)家有可能擴展這種毒素的治療用途,。目前，A型肉毒桿菌神經(jīng)毒素（商標名是Botox）被用于化妝品和治療神經(jīng)肌肉疾病，諸如眼瞼痙攣和過度出汗。這種毒素分裂僅見于神經(jīng)元的信使酶,，這阻止了細胞之間的相互通信并最終導(dǎo)致了麻痹,。
Joseph Barbieri 和Sheng Chen修改了E型肉毒桿菌神經(jīng)毒素的一個氨基酸基本單元，這可以讓它分裂一種稱為SNAP23的蛋白質(zhì),，該蛋白質(zhì)與神經(jīng)元信使酶非常接近,。這組作者把這種神經(jīng)毒素基因插入到了人類細胞中，結(jié)果發(fā)現(xiàn)它分裂了自然產(chǎn)生的SNAP23,，因此阻止了非神經(jīng)細胞之間的通信,。通過使用一種催化劑向培養(yǎng)的人類細胞中提供這種修改后的蛋白質(zhì)，這組作者還能夠分裂這些細胞中的SNAP23,。含有修改后的肉毒桿菌毒素基因或蛋白質(zhì)的細胞分泌更少的粘液和更少量的一種免疫系統(tǒng)信號傳導(dǎo)分子,。這組作者得出結(jié)論說，利用一種經(jīng)過修改的肉毒桿菌神經(jīng)毒素瞄準SNAP23可能有助于醫(yī)生治療其他疾病,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS June 1, 2009, doi: 10.1073/pnas.0903111106
Engineering botulinum neurotoxin to extend therapeutic intervention
Sheng Chen and Joseph T. Barbieri,1
Clostridium botulinum neurotoxins (BoNTs) are effective therapeutics for a variety of neurological disorders, such as strabismus, blepharospam, hemificial spasm, and cervical dystonia, because of the toxin's tropism for neurons and specific cleavage of neuronal soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNARE) proteins. Modifying BoNT to bind nonneuronal cells has been attempted to extend therapeutic applications. However, prerequisite to develop nonneuronal therapies requires the retargeting the catalytic activity of BoNTs to nonneuronal SNARE isoforms. Here, we reported the engineering of a BoNT derivative that cleaves SNAP23, a nonneuronal SNARE protein. SNAP23 mediates vesicle-plasma membrane fusion processes, including secretion of airway mucus, antibody, insulin, gastric acids, and ions. This mutated BoNT/E light chain LC/E(K224D) showed extended substrate specificity to cleave SNAP23, and the natural substrate, SNAP25, but not SNAP29 or SNAP47. Upon direct protein delivery into cultured human epithelial cells, LC/E(K224D) cleaved endogenous SNAP23, which inhibited secretion of mucin and IL-8. These studies show the feasibility of genetically modifying LCs to target a nonneuronal SNARE protein that extends therapeutic potential for treatment of human hypersecretion diseases.
