Author(s): Dolly O
Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors. Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis. Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin. Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine. There are 7 serotypes of this toxin-A, B, C1, D, E, F, and G-and each cleaves a different intracellular protein or the same target at distinct bonds. The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation. This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/12887390
Author(s): Mahowald ML1, Singh JA, Dykstra D
Author(s): Singh JA1, Mahowald ML, Noorbaloochi S
Author(s): Domsic RT1, Saltzman CL
Author(s): Kitaoka HB1, Alexander IJ, Adelaar RS, Nunley JA, Myerson MS, et al.
Author(s): Hurvitz EA1, Richardson JK, Werner RA, Ruhl AM, Dixon MR
Author(s): Podsiadlo D, Richardson S
Author(s): Boon AJ1, Smith J, Dahm DL, Sorenson EJ, Larson DR, et al.
Author(s): Chou CL1, Lee SH, Lu SY, Tsai KL, Ho CY, et al.
Author(s): Mense S
Author(s): Mahowald ML1, Krug HE, Singh JA, Dykstra D
Author(s): Schaible HG1, Del Rosso A, Matucci-Cerinic M
Author(s): Schaible HG1, Schmelz M, Tegeder I
Author(s): Schaible HG
Author(s): Welch MJ1, Purkiss JR, Foster KA
Author(s): Aoki KR
Author(s): Durham PL1, Cady R, Cady R
Author(s): Fisher NM1, Pendergast DR
Author(s): Hassan BS1, Mockett S, Doherty M