Unknown

Dataset Information

0

Choroid plexus megalin is involved in neuroprotection by serum insulin-like growth factor I.


ABSTRACT: The involvement of circulating insulin-like growth factor I (IGF-I) in the beneficial effects of physical exercise on the brain makes this abundant serum growth factor a physiologically relevant neuroprotective signal. However, the mechanisms underlying neuroprotection by serum IGF-I remain primarily unknown. Among many other neuroprotective actions, IGF-I enhances clearance of brain amyloid beta (Abeta) by modulating transport/production of Abeta carriers at the blood-brain interface in the choroid plexus. We found that physical exercise increases the levels of the choroid plexus endocytic receptor megalin/low-density lipoprotein receptor-related protein-2 (LRP2), a multicargo transporter known to participate in brain uptake of Abeta carriers. By manipulating choroid plexus megalin levels through viral-directed overexpression and RNA interference, we observed that megalin mediates IGF-I-induced clearance of Abeta and is involved in IGF-I transport into the brain. Through this dual role, megalin participates in the neuroprotective actions of IGF-I including prevention of tau hyperphosphorylation and maintenance of cognitive function in a variety of animal models of cognitive loss. Because we found that in normal aged animals, choroid plexus megalin/LRP2 is decreased, an attenuated IGF-I/megalin input may contribute to increased risk of neurodegeneration, including late-onset Alzheimer's disease.

SUBMITTER: Carro E 

PROVIDER: S-EPMC6725866 | biostudies-literature | 2005 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Choroid plexus megalin is involved in neuroprotection by serum insulin-like growth factor I.

Carro Eva E   Spuch Carlos C   Trejo Jose Luis JL   Antequera Desiré D   Torres-Aleman Ignacio I  

The Journal of neuroscience : the official journal of the Society for Neuroscience 20051101 47


The involvement of circulating insulin-like growth factor I (IGF-I) in the beneficial effects of physical exercise on the brain makes this abundant serum growth factor a physiologically relevant neuroprotective signal. However, the mechanisms underlying neuroprotection by serum IGF-I remain primarily unknown. Among many other neuroprotective actions, IGF-I enhances clearance of brain amyloid beta (Abeta) by modulating transport/production of Abeta carriers at the blood-brain interface in the cho  ...[more]

Similar Datasets

| S-EPMC2751559 | biostudies-literature
| S-EPMC3737068 | biostudies-literature
| S-EPMC9626938 | biostudies-literature
2019-05-01 | GSE126327 | GEO
| S-EPMC2639535 | biostudies-literature
2013-02-05 | E-GEOD-27630 | biostudies-arrayexpress
| S-EPMC10529429 | biostudies-literature
2022-12-15 | GSE218188 | GEO
| S-EPMC8785037 | biostudies-literature
| S-EPMC3042978 | biostudies-literature