title: Targeting blood-brain-barrier transcytosis - perspectives for drug delivery.
abstract: Efficient transcytosis across the blood-brain-barrier (BBB) is an important strategy for accessing drug targets within the central nervous system (CNS). Despite extensive research the number of studies reporting successful delivery of macromolecules or macromolecular complexes to the CNS has remained very low. In order to expand current research it is important to know which receptors are selective and abundant on the BBB so that novel CNS-targeting antibodies or other ligands could be developed, targeting those receptors for transcytosis. To do that, we have set up a proteomics- and transcriptomics-based workflow within the COMPACT project (Collaboration on the Optimization of Macromolecular Pharmaceutical Access to Cellular Targets) of the Innovative Medicines Initiative (IMI) of the EU. Here we summarise our overall strategy in endothelial transcytosis research, describe in detail the related challenges, and discuss future perspectives of these studies. This article is part of the Special Issue entitled "Beyond small molecules for neurological disorders".
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; Institute of Technology, University of Tartu, Tartu, Estonia. Electronic address: imre.mager@dpag.ox.ac.uk.
authors: Imre
authors: I
authors: Mäger
authors: Neuroscience Discovery, AbbVie Deutschland GmbH & Co. KG, Ludvigshafen, Germany.
authors: Axel H
authors: AH
authors: Meyer
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
authors: Jinghuan
authors: J
authors: Li
authors: Target Discovery Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.
authors: Martin
authors: M
authors: Lenter
authors: Target Discovery Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.
authors: Tobias
authors: T
authors: Hildebrandt
authors: Target Discovery Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.
authors: German
authors: G
authors: Leparc
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
authors: Matthew J A
authors: MJA
authors: Wood
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000502:physiology*; D016503:Drug Delivery Systems; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D057900:Transcytosis / Q000187:drug effects / Q000502:physiology*
chemical_list: D026901:Membrane Transport Proteins
keywords: Blood-brain-barrier; Drug delivery; Next generation; Proteomics; Sequencing; Transcytosis