SNAP-8

SNAP-8 Related Research

1.Physiological Background: Molecular Basis of Neuromuscular Contraction

Under normal physiological conditions, the neurotransmitter responsible for contraction of facial expression muscles is acetylcholine(ACh).

This is dependent on a protein complex called SNARE (Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor).

The complex is composed of a triad of proteins including SNAP-25 and Syntaxin at the presynaptic membrane, and VAMP on the vesicle membrane.

When these three forms assemble properly, they create a stable “molecular zippper” that pulls the vesicles containing acetylcholine towards the presynaptic membrane, where they fuse and release neurotransmitter into synapse’s cleft to cause muscle contraction.

2.Anti-wrinkle Mechanism of SNAP-8

Anti-wrinkle Mechanism of SNAP-8 The anti-wrinkle activity of SNAP-8 is also based on its competition with the SNARE complex2.

More specifically, the process is as follows:

(1).Competitive Inhibition

The amino acid sequence of SNAP-8 is patterned after the N-terminal region of the SNAP-25 protein.

So when SNAP-8 enters the skin and comes into contact with terminal nerve endings it can “mimic” itself as a section of the SNAP-25 protein, and in competition take up the space that would usually be claimed by SNAP-25 in the SNARE complex.

This prevents the complete assembly of the SNARE complex with its partner proteins such as Syntaxin and VAMP3.

(2).Blockade of Neurotransmitter Release

The conformational instability of the SNARE complex triggered by SNAP-8 binding results in a poor efficiency of vesicle fusion with the presynaptic membrane, so that acetylcholine is released at radically reduced levels.

Nerve transmissions are weakened, which means less contraction signals are sent to facial muscles and thus muscle relaxation occurs.

This relaxing of the muscle leads toward a depth and length in expression lines (crow’s feet, forehead, glabellar), which can be avoided to prevent new-wrinkles.

In vitro studies have demonstrated that 1.5 mM SNAP-8 can inhibit 43% of glutamate release, and it can decrease the depth of wrinkles caused by wrinkle-inducing agents by an estimated 30–62% in clinical trials4.

(3).Synergy Amplification

In vitro evaluations reveal that SNAP-8 and Leuphasyl work independently but collaboratively on synergism.

They shared inhibitory activities of 38% and 7%, respectively, in relevant inhibition assays.

When tested simultaneously at equimolar doses (0.75 mM), the maximal inhibition was 47%2.

3.Experimental and Clinical Research Evidence

Research Lipotec S.A.U. the manufacturer of SNAP-8, have published studies to provide evidence of its performance.

The in vitro experiments demonstrate SNAP-8 could partly inhibit SNARE complex formation and stabilize acetylcholine release.

In in vivo clinical studies, the evaluation by techniques such as silicone replica analysis after application of formulations with SNAP-8 for a time period resulted in a significant reduction in the depth of wrinkles (a maximum 63.13% was recorded in one study).

These results represent the first direct commercial evidence of SNAP-85 anti-wrinkle activity.

4.Mechanistic Comparison with Botulinum Toxin Type A

The action mechanism of SNAP-8 is very similar to that of Botulinum Toxin Type A (BoNT/A).

Both have in common that they act on the SNARE complex.

But the basic difference remains in action and safety.

BoNT/A is a protease that causes irreversible cleavage of SNAP-25 protein and thus totally eliminates the activity of the SNARE complex.

Whereas SNAP-8 does its work by competing, results in the inhibition of exocytosis which is both reversible and less severe.

BoNT/A is an injectable drug which carries risks such as nerve paralysis and stiffness of the face, for which proper doctor should be responsible.

SNAP-8, however, is used topically and affects only the epidermis and dermis rather than being administered through an injection,and therefore involve no associated risks, furthermore more convenient.

This makes it a highly convenient and safer alternative.

5.Conclusion and Outlook

In conclusion, as an emerging active ingredient in cosmetic industry, SNAP-8 shows good anti-wrinkle activity by acting on release (chemo/exocytosis) of neurotransmitter acetylcholine, wherein it has been verified to reduce the formation of SNARE complex competitively with SNAP-25 thereby blocking glutamate release and reducing muscle contraction.

This concept is similar to Botulinum Toxin but provides a non-invasive approach.

The skin permeation and efficacy of such peptides is thought to be further enhanced by technologies such as nanoencapsulation6.