Proteomics and the blood–brain barrier: how recent findings help drug development

ABSTRACT

The drug discovery and development processes are divided into different stages separated by milestones to indicate that significant progress has been made and that certain criteria for target validation, hits, leads and candidate drugs have been met. Proteomics is a promising approach for the identification of protein targets and biochemical pathways involved in disease process and thus plays an important role in several stages of the drug development. The blood–brain barrier is considered as a major bottleneck when trying to target new compounds to treat neurodegenerative diseases. Based on the survey of recent findings and with a projection on expected improvements, this report attempt to address how proteomics participates in drug development.

KEYWORDS:

• Blood–brain barrier
• brain capillary endothelial cells
• neurovascular unit
• drug development
• proteomics

Acknowledgments

The authors thank Roméo Cecchelli (Université d’Artois, Lens, France) for his critical reading of the paper.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• The blood–brain barrier (BBB) is constituted of an assembly of cells: endothelial cells, pericytes, astrocytes, and neurons, forming the neurovascular unit. Each actor of this unit plays a role on the barrier functions and could be targeted specifically

• The BBB is a dynamic barrier protecting the brain and limiting the entrance of compound originally destined to treat central nervous system disorders. Different strategies, described in this review, could be applied to cross the BBB.

• With the information provided by proteomics studies, a thorough understanding of the BBB becomes more and more achievable.

• Proteomic tools provide insight at several levels including, but not limited to, the protein pattern expressed by the BBB cells, the quantity of receptors expressed at the surface of the brain capillaries, and the interaction of proteins with other proteins or ligand.

• A more thorough knowledge of the BBB will provide new strategies to reach the brain compartment.

• Pharmaceutical industry and applied research work to produce drugs and ways of administration that allow the access to the brain on one hand and understand the mechanism involved in the protection of the brain by the BBB on the other hand.

• New ways of targeting the brain are constantly tested and brought up to light in order to help pharmaceutical industry to overcome the limitations imposed by the BBB.