¯S§Oªº¬O¥¦¬ã¨sAPOPTOSISªº¤èªk, °£¤F¤@¯ëªºapoptosis%(TUNEL assay), DNA ladderring, ÁÙ±q¥t¤@¨¤«×¤Á¤J: Caspaseªºsubstrate¤À¸Ñª«DEVDªº¬¡©Ê, ¨Ã¨Ï¥Î¤@¨ÇCaspase inhibitor¦p zVAD-fluoromethylketone (fmk)

±µ¤U¨Ó¦]¬°¯«¸gÅÜ©Ê·|¨Ï±otau³J¥Õ½è¤£¥¿±`phosphorylation, ¦]¦¹¥i¥H¥Îantibody(AT-8¡Vlike antibody 11b directed against the phosphorylated epitope S202-205)¨Ó´ú¥¦ªº¶q¬O§_¼W°ª, ¦p¤U¹Ï:

 ¥ª¹Ï¥i¨£neurite(¤]´N¬Ocell cultureùتºaxon or dendrite), ¤£ºÞactin or tubulin³£¶}©l²£¥Íenlarged varicosities, bulbªº²{¶H. ¥ª¹Ï¤U¤]¬Ý¨ì±q­ì¥»ªº very diffuse ¨ì highly fluorescent, punctuate staining, ³o·N¨ýµÛ a disorganization/aggregation of tau filaments

@ Lowe NJ et al. Double-blind, randomized, placebo-controlled, dose-response study of the safety and efficacy of botulinum toxin type A in subjects with crow's feet. Dermatol Surg. 2005;31(3):257-62

RESULTS: A dose-dependent treatment effect for efficacy was observed, with higher doses having an increased magnitude and duration of effect. However, a clear differentiation between the 18 U and 12 U doses was not apparent. Few adverse events were reported, with no statistically significant differences between BTX-A and placebo in the incidence of subjects experiencing adverse events. CONCLUSION: 12 U per side suggested as the most appropriate dose.

@ ¦×¬r±ìµßªº¾AÀ³¯g: Arq Neuropsiquiatr 2005;63(1):180-185

1, Movement Disorders: Dystonia, Hemifacial Spasm, Tremor, Tics, Bruxism, Re-innervation Synkinesias, Myokymia, Neuromyotonia, Stiff Person Syndrome
2, Spasticity
3, Hypersecretory Disorders
4, Hyperhidrosis: Sialorrhea, Hyperlacrimation, Rhinorrhea
5, Ophtalmic Disorders: Strabismus, Nystagmus, Exotropia, Esotropia, Entropium, Protective Ptosis
6, Pain: Tension Headache, Migraine, Myofacial Pain
7, Pelvic Floor and Gastrointestinal Disorders: Achalasia, Anal Fissures, Detrusor-Sphincter Dyssynergia, Vesical Sphincter Spasms, Sphyncter Odii Spasms, Anismus, Vaginismus
8, Cosmetic Applications: Muscular Facial Lines, Facial Assymetries
9, Others: Eye-Lid Opening Apraxia, Tetanus, Stuttering, Perioperative Fixations in Orthopedic Surgery

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Botulinum toxin has a high affinity for the neuromuscular junction,
where motor nerve endings containing acetylcholine-filled synaptic vesicles come in close contact with muscle fibers. Under normal circumstances, synaptic vesicles fuse with the neural cell membrane and release their contents into the synaptic space through a calcium-dependent process known as exocytosis. Muscle contraction ensues when acetylcholine traverses the synaptic space and binds to receptors on muscle cells.
Docking of synaptic vesicles with the neural cell membrane is facilitated
by a complex of proteins known as ¡§Soluble N-ethylmaleimide-sensitivefactor Attachment Protein Receptor¡¨(SNARE) proteins, which include a 25-kD synaptosomal-associated protein (SNAP-25), vesicle-associated membrane protein (VAMP, or synaptobrevin), and syntaxin.

These proteins anchor the vesicle membrane to the neural cell membrane by linking to form what is known as a synaptic fusion complex. Botulinum toxin induces reversible cholinergic blockade at the neuromuscular junction (i.e., chemical denervation) by inhibiting vesicle exocytosis, thereby reducing acetylcholine release into the synapse and muscle contraction. The toxin first binds to acceptors (i.e., receptors) in the neural cell membrane, and the toxin then is internalized in the neural cell. The acceptors have not yet been identified, but they appear to vary for the different serotypes. The botulinum toxin heavy chain is responsible for binding to the acceptor and subsequent endocytosis. During this process, the neural cell plasma membrane invaginates around the toxin-receptor complex, forming a toxin-containing vesicle within the neural cell. The vesicle then releases the light chain, a zinc dependent endopeptidase (i.e., metalloprotease) that cleaves SNARE proteins, thereby interfering with vesicle docking and exocytosis. The enzymatic activity of the light chain depends on the serotype. Serotype A cleaves SNAP-25, and serotype B cleaves VAMP.8 All botulinum toxins inhibit vesicle exocytosis and muscle contraction. They do not affect the synthesis or storage of acetylcholine or the conduction of electrical signals along the nerve fiber.
The effect of botulinum toxin is only temporary because collateral axonal sprouts develop over time at the nerve terminal. (de Paiva A, et al. Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci U S A. 1999;
96:3200-5.) These sprouts can release acetylcholine into the synaptic space so that muscle activity returns. The motor end plate eventually regains normal function, and the nerve sprouts then regress. These phenomena explain why repeated administration of botulinum toxin may be required to maintain a therapeutic effect.