Persistence of Botulinum Neurotoxin A Subtypes 1-5 in Primary Rat Spinal Cord Cells

被引：63
|
作者：
Whitemarsh, Regina Clare Meyer [1 ]
Tepp, William Howard [1 ]
Johnson, Eric Arthur [1 ]
Pellett, Sabine [1 ]
机构：
[1] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA
来源：
PLOS ONE | 2014年 / 9卷 / 02期
关键词：
CLOSTRIDIUM-BOTULINUM; GENETIC DIVERSITY; LIGHT-CHAIN; TOXIN; PURIFICATION; SEROTYPES; NEURONS; STRAIN; LOCALIZATION; RECOVERY;
D O I：
10.1371/journal.pone.0090252
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Botulinum neurotoxins (BoNTs) are the most poisonous substances known and cause the severe disease botulism. BoNTs have also been remarkably effective as therapeutics in treating many neuronal and neuromuscular disorders. One of the hallmarks of BoNTs, particularly serotype A, is its long persistence of 2-6 months in patients at concentrations as low as fM or pM. The mechanisms for this persistence are currently unclear. In this study we determined the persistence of the BoNT/A subtypes 1 through 5 in primary rat spinal neurons. Remarkably, the duration of intracellular enzymatic activity of BoNT/A1, /A2, /A4 and /A5 was shown to be at least 10 months. Conversely, the effects of BoNT/A3 were observed for up to,5 months. An intermittent dosing with BoNT/E showed intracellular activity of the shorter acting BoNT/E for 2-3 weeks, followed by reoccurrence and persistence of BoNT/A-induced SNAP-25 cleavage products.
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页数：6
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