Albumin-blunted deleterious effect of amyloid-beta by preventing the internalization of the peptide into neurons.
Amyloid-beta (A beta) is the main component of senile plaques, one of the hallmarks of Alzheimer's disease. Our results showed that A beta(25-35) decreased neuronal viability while it increased generation of reactive oxygen species (ROS). Under these circumstances, albumin (BSA) prevented ROS production and neuronal death in a dose- and time-dependent manner. In addition, BSA partially prevented the decrease in the expression of GAP-43, MAP-2, and tubulin, and the phosphorylation of tau protein caused by A beta, suggesting that BSA protects against the loss of plasticity caused by the peptide. Our findings suggest that BSA exerts its protective effect by binding to A beta in an equimolecular way, which prevents heterodimer (A beta-BSA) entry into neurons. In fact, BSA prevented A beta internalization, as shown by confocal immunocytochemistry, suggesting that BSA causes its protective effect by sequestrating A beta, which cannot reach its intracellular targets. This is consistent with the idea that A beta must enter neurons to exert its deleterious effects.
Vega
Lourdes
L
Department of Biochemistry and Molecular Biology, Instituto de Neurociencias de Castilla y León (INCYL), University of Salamanca, Spain.
Arroyo
Angel A
AA
Tabernero
Arantxa
A
Medina
José M
JM
D000418:Albumins / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D019922:GAP-43 Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D000418:Albumins; D016229:Amyloid beta-Peptides; D019922:GAP-43 Protein; C521921:GAP-43-3 protein; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D014404:Tubulin; D016875:tau Proteins