The Cargo Strategy As A Key Tool In Neuroprotection
The possibility to target protein complexes and enzymes involved in intracellular signalling pathways by means of cell permeable peptide (CPP) conjugates represents a novel, versatile and extremely powerful way of blocking the propagation of intracellular signalling events or intracellular processes, with an unprecedented specificity allowing for reduction of side effects.
D-JNKI1 is a cell-permeable, biologically-active peptide consisting of a carboxyl terminal sequence derived from the JNK binding domain of the scaffold protein JIP-1/IB1 (JBD20), and an amino terminal portion containing the HIV-TAT 48-57 transporter sequence (Bonny et al., 2001). D-JNKI-1 has been designed to block the interaction, mediated by JBD domain, between JNK and its targets.
D-JNKI1 afforded powerful protection against NMDA excitotoxicity in cortical neurons and against cerebral ischemia in vivo (Borsello et al., 2003), as well as in two other neurodegenerative models (hair-cell loss in animal models of sudden deafness (Wang et al., 2003) and retinal ganglion cell loss following optic nerve crush in vivo (Tezel et al., 2004)).
The peptide progressed in clinical trails for preventing brain ischemia/stroke (see CHUV/Xigenpharma Lausanne web-link).
Research Participants:
Tiziana Borsello
Xenia Antoniou, PhD
Marco Feligioni
Alessio Colombo
Mariaelena Repici
Cristina Ploia
Alessandra Sclip
Daniele Cardinetti
Alice Perego