title: Alleviation of abnormal synaptic neurotransmitter release by cell-permeable form of the truncated SNAP-25 upon transcutaneous delivery.
abstract: 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.
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Translational Research Center for Protein Function Control, Yonsei University, Seoul, Republic of Korea.
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Park
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Shin
authors.forename: Sung-Dong
authors.initials: SD
authors.lastname: Park
authors.forename: Sang-Kyou
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000200:Action Potentials; D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010243:Paralysis / Q000139:chemically induced; D017434:Protein Structure, Tertiary; D011817:Rabbits; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology*; D012869:Skin Absorption / Q000187:drug effects; D015595:Skin Aging / Q000187:drug effects; D013552:Swine; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology*
chemical_list: D002395:Catecholamines; D018377:Neurotransmitter Agents; D011993:Recombinant Fusion Proteins; D050825:Synaptosomal-Associated Protein 25