Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

<p>Abstract</p> <p>Background</p> <p>Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.</p> <p>Results</p> <p>We fused the signal peptide from the Von Willebrand Factor (VWF) to a furin site followed by a processed form of the Agouti related protein (AgRP), AgRP_83-132or α-melanocyte stimulating hormone. <it>In vitro</it>, these minigenes were secreted and biologically active. Additionally, the proteins of the minigenes were not transported into projections of primary neurons, thereby ensuring local release. <it>In vivo </it>administration of VWF-AgRP_83-132, using an adeno-associated viral vector as a delivery vehicle, into the paraventricular hypothalamus increased body weight and food intake of these rats compared to rats which received a control vector.</p> <p>Conclusions</p> <p>This study demonstrated that removal of the N-terminal part of full length AgRP and addition of a VWF signal peptide is a successful strategy to deliver neuropeptide minigenes to the brain and establish local neuropeptide secretion.</p