ANTI-AGING 23
Expression lines targeted via both synaptic pathways
Míriam Mateu, Ariadna Grau-Campistany, Silvia Pastor, Patricia Carulla, Julia A. Boras, Mikel Gorostiaga – LipoTrue, Spain
An excess of repeated contraction of the muscles involved in facial expressions results in the appearance of fine lines known as expression wrinkles. Skeletal muscle contraction is controlled by impulses from the central nervous system via the Neuromuscular Junctions (NMJs). Neurons receive chemical signals that produce changes in the membrane potential (depolarization). When depolarization is large enough, it is converted into an action potential that spreads along the axons. Then, a Ca2+
triggers the fusion of secretory vesicles, filled with neurotransmitters, with the plasma membrane. This fusion is mediated by the concerted action of the SNARE protein family (syntaxin, VAMP and SNAP- 25) and Munc18-1 protein.1
Munc18-1 binds to syntaxin helping to initiate the assembly of the SNARE complex forcing the vesicle to move closer to the neuronal membrane for their fusion.1,2 Munc18-1 has been reported to initiate and act on the folding intermediates of SNARE to chaperone and stabilize its assembly.3
It
is also thought to mediate vesicle docking and fusion and even shaping fusion pore kinetics.2
After the fusion, the Acetylcholine (ACh) neurotransmitter is released into the
influx
Figure 1: Munapsys modulates both pre- and post-synaptic pathways.
synapse, and it travels to the muscle membrane to associate with its clustered receptor (AChRs) and trigger the post- synaptic pathway. Clustering of AChR is induced by the proteoglycan agrin which binds to the transmembrane receptor LRP4 activating the muscle-specific kinase (MuSK) receptor that, together with AChR associated protein rapsyn, causes AChR clustering.4 Rapsyn also links AChRs to the utrophin- associated complex, which appears to be required for AChR stabilization.5
If sufficient ATP is present, myosin binds to actin to begin cross-bridge and sliding (the sarcomere shortens and the muscle contracts). In the absence of calcium, this binding does not occur, so the presence of free calcium is a key regulator of muscle contraction.7 Botulinum toxin treatments have lived together with cosmetic ingredients acting in the pre-synaptic or the post-synaptic pathways to relax muscle contraction and improve the fine lines.
ACh and AChR interaction opens a cationic channel in the AChR causing a localized depolarisation and then triggering an action potential. This depolarization triggers the release of calcium from the sarcoplasmic reticulum to the sarcoplasm where it binds to the troponin protein unblocking the myosin-binding sites on actin.6
Munapsys™ is a novel botulinum toxin- like peptide obtained by in silico design. It is the first cosmetic ingredient able to act both in the pre- and post-synaptic pathways of muscle contraction. Pre-synaptic: Munapsys competes with Munc-18 for its position in syntaxin, obstructing SNARE complex assembly and the release of ACh into the synapse. Post-synaptic: Munapsys modulates AChR clustering, depolarisation, Ca2+
mobilisation, and actomyosin cross-
Figure 2: Myosin (green) decrease in human mature skeletal myocytes treated with Munapsys. May 2019 PERSONAL CARE NORTH AMERICA
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