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Megalin mediates the transport of leptin across the blood-CSF barrier

Dietrich, Marcelo O., Spuch, Carlos, Antequera, Dessire, Rodal, Izaskun, de Yébenes, Justo G., Molina, José Antonio, Bermejo, Felix, Carro, Eva·2008·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2007.01.008
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Abstract

Leptin, a peptide hormone secreted by adipose tissue, exhibits a large range of central and peripheral actions. It has been proposed that the participation of leptin in diseases such as obesity is due to, at least in part, its impaired transport across the blood-brain barrier (BBB). Since, the mechanisms by which brain takes up leptin remain unclear, we set out to study how leptin may cross the BBB. We have used different immunoassays and lentiviral vectors to analyze the role of megalin in the transport of leptin in rodents and humans. We demonstrate that circulating leptin is transported into the brain by binding to megalin at the choroid plexus epithelium. Indeed, the downregulation of megalin expression in physiological and pathological situations such as aging and Alzheimer's disease was correlated with poor entry of leptin into the brain. Moreover, amyloid beta (Abeta) deposits of choroid plexus could be disturbing megalin function. The present data indicate that leptin represents a novel megalin ligand of importance in the levels and therapeutic actions of leptin into the brain.

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Metadata

Authors
Dietrich, M. O., Spuch, C., Antequera, D., Rodal, I., de Yébenes, J. G., Molina, J. A., Bermejo, F., & Carro, E.
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2008-06
Volume
29
Issue
6
Pages
902-912
ISSN
0197-4580
DOI
10.1016/j.neurobiolaging.2007.01.008
Cited by
172
References
5
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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