Targeting the brain: blood-to-brain transport of lipidized neuropeptides, potential therapeutics

Neuropeptides, e.g. anorexigenic prolactin-releasing peptide (PrRP) or cocaine-and amphetamine-regulated transcript peptide (CARTp), are promising therapeutics for the treatment of obesity or neurodegeneration. After central intracerebroventricular application, both peptides significantly decreased food intake in fasted mice. However, no observable effect was monitored after their peripheral administration. Peripheral application of lipidized analogs of the mentioned neuropeptides significantly decreased food intake in mice, and lowered body weight of obese mice after chronic application, pointing to their blood-to brain transport.

PhD project will explore the mechanisms involved in the transport of the new lipidized analogs to the brain, using peptide analogs with fluorescent or ¹²⁵I labels. Different in vitro models of the blood-brain barrier (BBB) will be employed, such as primary endothelial cells cultivated on the transwell system. Further, interactions between the lipidized neuropeptides and tanycytes will be studied. Tanycytes are thought to play a key role in transport of nutrients and other molecules across the BBB. We plan to determine whether peptides are transported to the brain by the tanycytes in vivo, using mice with a selectively disrupted tanycytic transport.

Field of study: Biochemistry and pathobiochemistry