tetanus toxin c-fragment the courier and the cure破伤风毒素c-fragment信使和治疗.pdfVIP

Toxins 2010, 2, 2622-2644; doi:10.3390/toxins2112622 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Tetanus Toxin C-Fragment: The Courier and the Cure? Janne M. Toivonen, Sara Oliván and Rosario Osta * LAGENBIO-I3A, Veterinary School, Aragón Institute of Health Sciences (IACS), Universidad de Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain; E-Mails: jtoivonen.iacs@aragon.es (J.M.T.); soligar@unizar.es (S.O.) * Author to whom correspondence should be addressed; E-Mail: osta@unizar.es; Tel.: +34-976-761-621; Fax: +34-976-761-612. Received: 11 October 2010 / Accepted: 28 October 2010 / Published: 29 October 2010 Abstract: In many neurological disorders strategies for a specific delivery of a biological activity from the periphery to the central nervous system (CNS) remains a considerable challenge for successful therapy. Reporter assays have established that the non-toxic C-fragment of tetanus toxin (TTC), provided either as protein or encoded by non-viral naked DNA plasmid, binds pre-synaptic motor neuron terminals and can facilitate the retrograde axonal transport of desired therapeutic molecules to the CNS. Alleviated symptoms in animal models of neurological diseases upon delivery of therapeutic molecules offer a hopeful prospect for TTC therapy. This review focuses on what has been learned on TTC-mediated neuronal targeting, and discusses the