Gelsolin restores A beta-induced alterations in choroid plexus epithelium.
Histologically, Alzheimer's disease (AD) is characterized by senile plaques and cerebrovascular amyloid deposits. In previous studies we demonstrated that in AD patients, amyloid-beta (A beta) peptide also accumulates in choroid plexus, and that this process is associated with mitochondrial dysfunction and epithelial cell death. However, the molecular mechanisms underlying A beta accumulation at the choroid plexus epithelium remain unclear. A beta clearance, from the brain to the blood, involves A beta carrier proteins that bind to megalin, including gelsolin, a protein produced specifically by the choroid plexus epithelial cells. In this study, we show that treatment with gelsolin reduces A beta-induced cytoskeletal disruption of blood-cerebrospinal fluid (CSF) barrier at the choroid plexus. Additionally, our results demonstrate that gelsolin plays an important role in decreasing A beta-induced cytotoxicity by inhibiting nitric oxide production and apoptotic mitochondrial changes. Taken together, these findings make gelsolin an appealing tool for the prophylactic treatment of AD.
Vargas
Teo
T
Neuroscience Laboratory, Research Center, Hospital 12 de Octubre, Avenida de Córdoba, 28041 Madrid, Spain.
Antequera
Desiree
D
Ugalde
Cristina
C
Spuch
Carlos
C
Carro
Eva
E
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002457:Cell Extracts / Q000737:chemistry / Q000494:pharmacology; D002831:Choroid Plexus / Q000187:drug effects* / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D018260:Gelsolin / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D002457:Cell Extracts; D018260:Gelsolin; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D009569:Nitric Oxide