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Alleviation of abnormal synaptic neurotransmitter release by cell-permeable form of the truncated SNAP-25 upon transcutaneous delivery

2013; Elsevier BV; Volume: 543; Linguagem: Inglês

10.1016/j.neulet.2013.02.055

1872-7972

Tae Yoon Park, Min-Jung Shin, Sung-Dong Park, Sang‐Kyou Lee,

Neurological disorders and treatments

Abnormal releases of neurotransmitters result in movement disorders such as dystonia, chorea, tics, blepharospasm and wrinkle formation, and intra-muscular injection of Botulinum neurotoxin is widely used for the treatment of these complications. But it is potentially poisonous and must be intra-muscularly injected with precision by a well-trained physician. For novel therapeutic development with high safety profile and easy skin penetration for these complications, we generated Trans-X, a cell permeable form of the truncated SNAP-25 that is one of the SNARE complex for vesicle exocytosis of neuron. Upon topical administration, Trans-X efficiently penetrated through skin, reached the dermis layer and remained stable. Trans-X, which did not show any ocular or skin allergic sensitivity, can block the pre-synaptic neurotransmitter transport via acting as a competitive inhibitor of SNARE complex formation, and effectively induced muscle paralysis comparable to BOTOX® evaluated by measuring compound muscle action potential. Topical treatment of the facial skin with Trans-X in clinical study can prevent the wrinkle formation and improve the skin roughness. Therefore, our study suggests that Trans-X may be a convenient and effective medical and cosmetic treatment for local management of movement disorder without systemic toxicity.