ANTI-AGEING 137
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 (depolarisation). When depolarisation 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 stabilise 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
ACh and AChR interaction opens a cationic channel in the AChR causing a localised depolarisation and then triggering an action potential. This depolarisation 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
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 stabilisation.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.
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. April 2019 PERSONAL CARE EUROPE
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122 |
Page 123 |
Page 124 |
Page 125 |
Page 126 |
Page 127 |
Page 128 |
Page 129 |
Page 130 |
Page 131 |
Page 132 |
Page 133 |
Page 134 |
Page 135 |
Page 136 |
Page 137 |
Page 138 |
Page 139 |
Page 140 |
Page 141 |
Page 142 |
Page 143 |
Page 144 |
Page 145 |
Page 146 |
Page 147 |
Page 148 |
Page 149 |
Page 150 |
Page 151 |
Page 152 |
Page 153 |
Page 154 |
Page 155 |
Page 156 |
Page 157 |
Page 158 |
Page 159 |
Page 160 |
Page 161 |
Page 162 |
Page 163 |
Page 164 |
Page 165 |
Page 166 |
Page 167 |
Page 168 |
Page 169 |
Page 170 |
Page 171 |
Page 172 |
Page 173 |
Page 174 |
Page 175 |
Page 176 |
Page 177 |
Page 178 |
Page 179 |
Page 180 |
Page 181 |
Page 182 |
Page 183 |
Page 184 |
Page 185 |
Page 186 |
Page 187 |
Page 188
