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Endocrine Regulation of Microvascular Receptor-Mediated Transcytosis and Its Therapeutic Opportunities: Insights by PCSK9-Mediated Regulation. | LitMetric

Endocrine Regulation of Microvascular Receptor-Mediated Transcytosis and Its Therapeutic Opportunities: Insights by PCSK9-Mediated Regulation.

Pharmaceutics

Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg, University Mainz, Duesbergweg 6, 55128 Mainz, Germany.

Published: April 2023

AI Article Synopsis

Article Abstract

Currently, many neurological disorders lack effective treatment options due to biological barriers that effectively separate the central nervous system (CNS) from the periphery. CNS homeostasis is maintained by a highly selective exchange of molecules, with tightly controlled ligand-specific transport systems at the blood-brain barrier (BBB) playing a key role. Exploiting or modifying these endogenous transport systems could provide a valuable tool for targeting insufficient drug delivery into the CNS or pathological changes in the microvasculature. However, little is known about how BBB transcytosis is continuously regulated to respond to temporal or chronic changes in the environment. The aim of this mini-review is to draw attention to the sensitivity of the BBB to circulating molecules derived from peripheral tissues, which may indicate a fundamental endocrine-operating regulatory system of receptor-mediated transcytosis at the BBB. We present our thoughts in the context of the recent observation that low-density lipoprotein receptor-related protein 1 (LRP1)-mediated clearance of brain amyloid-β (Aβ) across the BBB is negatively regulated by peripheral proprotein convertase subtilisin/kexin type 9 (PCSK9). We hope that our conclusions will inspire future investigations of the BBB as dynamic communication interface between the CNS and periphery, whose peripheral regulatory mechanisms could be easily exploited for therapeutic purposes.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144601PMC
http://dx.doi.org/10.3390/pharmaceutics15041268DOI Listing

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