In recent years, vast amounts of data on the mechanisms of neural de- and regeneration have accumulated. However, only in disproportionally few cases has this led to efficient
therapies for human patients. Part of the problem is to deliver cell death-averting genes or gene products across the blood-brain barrier (BBB) and cellular membranes. The discovery of Antennapedia (Antp)-mediated transduction of heterologous
proteins into cells in 1992 and other "Trojan horse
peptides" raised hopes that often-frustrating attempts to deliver
proteins would now be history. The demonstration that
proteins fused to the
Tat protein transduction domain (PTD) are capable of crossing the BBB may revolutionize molecular research and neurobiological
therapy. However, it was only recently that PTD-mediated delivery of
proteins with therapeutic potential has been achieved in models of neural degeneration in nerve
trauma and
ischemia. Several groups have published the first positive results using
protein transduction domains for the delivery of therapeutic
proteins in relevant animal models of human
neurological disorders. Here, we give an extensive review of
peptide-mediated
protein transduction from its early beginnings to new advances, discuss their application, with particular focus on a critical evaluation of the limitations of the method, as well as alternative approaches. Besides applications in neurobiology, a large number of reports using PTD in other systems are included as well. Because each
protein requires an individual purification scheme that yields sufficient quantities of soluble, transducible material, the neurobiologist will benefit from the experiences of other researchers in the growing field of
protein transduction.