๐ ็ธฝ็ฎ้ ๏ฝ ๐ ่ฑๆๅๆ๏ผๆฌ็ฏ๏ผ ๏ฝ ๐ ๅฎๆด็ฟป่ญฏ ๏ฝ โญ ็ฒพ่ฏ็ญ่จ
Neuromodulation
Neuromodulation
The most well-known function of BTX is its inhibition of acetylcholine (Ach) release at the presynaptic neuromuscular junction. This mechanism of action involves three discrete stages: binding, internalization, and prevention of neurotransmitter release.6 Both the 50-kDa and 100-kDa active components have unique roles in these stages. Binding of the presynaptic receptor is triggered by the 100-kDa heavy chain which then induces receptor-mediated endocytosis for internalization of the molecule. Once internalized, the 50-kDa light chain cleaves proteins that facilitate the docking of Ach at the presynaptic membrane, thus inhibiting its release. BTX serotypes A, C and E cleave synaptosomeโassociated protein-25 (SNAP-25) and serotypes B, D, F, and G cleave vesicleโassociated membrane protein (VAMP).
This presynaptic inhibition is temporary. Reversal occurs in two phases, explaining the gradual loss of clinical efficacy.7,8 Firstly, de novo nerve terminals sprout from the existing parent terminal axon during the first 28 days after BTX exposure, leading to the establishment of a nascent neuromuscular junction. Following this first phase, the parent terminal axon gradually synthesizes new SNAP-25 proteins with simultaneous regression and elimination of the new sprouts. This second phase takes place over the
next 3 months, which explains why the effects of BTX tend to dissipate around this timeframe.