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【原创摘要编译】科学家解释肉毒菌毒素如何攻
http://www.sciencedaily.com/releases/2004/12/041220013800.htm
http://www.stanford.edu/dept/news/pr/2004/pr-botox-0112.html
每年，有数以百万计的人们为了消除面部皱纹使得自己看起来更加年轻，注射肉毒菌毒素。这在美容业内人所共知。肉毒菌毒素是FDA批准的一种处方药，用于治疗不自主眨眼、斜视、不随意肌肉收缩和腋窝多汗等神经性症状。
然而，很多使用者并不了解肉毒菌素是一种细菌性的神经毒素。肉毒菌素的过量吸收，会导致瘫痪甚至死亡。上个月，几名欲去皱美容的弗罗里达的居民因接受注射肉毒菌素而住进了医院。
肉毒菌素的作用机理是，入侵神经细胞释放一种酶从而防止肌肉收缩。近年来，科学家确定了这种酶分子的结合靶点SNAREs，每分子与SNAREs在神经与肌肉之间的神经键处形成复合体。没有SNAREs，神经细胞不会释放指导肌肉收缩的化学信号分子。
斯坦福大学教授Axel T. Brunger说：“肉毒菌素选择性地攻击某一种SNARE并将其解裂成两个片段，这足以破坏SNARE的功能。然而肉毒菌素是如何识别并对SNARE进行切割，仍是一个谜团，需要进一步的研究思考。”
现在，Brunger和斯坦福的研究生Breidenbach部分地解开了这一谜团。他们的研究报告发表在12月12日“自然”杂志的网络版上。
Brunger期望着一研究成果能够更好地指导肉毒菌素的临床应用，包括治疗耳鸣和小便失禁等。同时他还希望下一步能够确定其它细菌毒素如破伤风毒素的结构，以利于指导开发治疗肉毒菌素中毒和破伤风的新型药物。
Date: 2004-12-23
Scientists Solve The Mystery Of How Botox Attacks Nerves And Eliminates Wrinkles
Every year, millions of people try to look younger by taking injections of Botox, a prescription drug that gets rid of facial wrinkles by temporarily paralyzing muscles in the forehead. Although best known as a cosmetic procedure, Botox injections also have been approved by the Food and Drug Administration (FDA) to treat uncontrolled blinking (blepharospasm), lazy eye (strabismus), involuntary muscle contractions in the neck (cervical dystonia) and acute underarm sweating (severe primary axillary hyperhidrosis).
Botox users might be surprised to learn that they're actually receiving minute injections of a bacterial neurotoxin called botulinum, one of the most poisonous substances known. Exposure to large amounts of botulinum bacteria can cause a paralytic, sometimes-fatal disease called botulism. Last month, several Floridians were hospitalized with botulism after receiving injections of an anti-wrinkle treatment that authorities suspect was a cheap, non-FDA-approved imitation of Botox.
The botulinum toxin works by invading nerve cells, where it releases an enzyme that prevents muscle contraction. In recent years, scientists have determined that the enzyme binds to specific sites on proteins called SNAREs, which form a complex in the synapse between nerve and muscle cells. Without SNAREs, nerves cannot release the chemical signals that tell muscle cells to contract, and paralysis results.
"The botulinum enzyme selectively attacks one of the SNARE proteins and cuts it into two pieces," said Stanford University Professor Axel T. Brunger. "That's sufficient to disrupt its function. But the means by which the enzyme identifies and cleaves its target SNARE has been a subject of much speculation."
Now, Brunger and Stanford graduate student Mark A. Breidenbach have solved part of the puzzle. Their results, which will be published in the Dec. 12 online edition of the journal Nature, could help researchers develop alternative treatments for botulism and perhaps find new medical applications for Botox and other neurotoxins.
Clever machinery
There are seven forms of botulinum neurotoxin produced by seven different strains of the Clostridium botulinum bacterium, explained Brunger, a Howard Hughes Medical Institute investigator who holds professorships in three Stanford departments梞olecular and cellular physiology, neurology and neurological sciences, and the Stanford Synchrotron Radiation Laboratory (SSRL).
"The seven botulinum neurotoxins cut SNARE proteins at different sites along the surface," he said. "Why that is, we really don't know exactly."
For the Nature study, the researchers focused on one of the seven forms, botulinum serotype A, which is the active ingredient in Botox. Breidenbach, lead author of the study, spent months in Brunger's lab trying to crystallize a SNARE/botulinum A complex for laboratory analysis. Unfortunately, the botulinum A samples usually ended up slicing the SNARE target in two, rendering it useless.
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作者:admin@医学,生命科学 2011-07-21 18:16
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