In vitro and in vivo degradation of Abeta peptide by peptidases coupled to erythrocytes.
It is generally believed that amyloid beta peptides (Abeta) are the key mediators of Alzheimer's disease. Therapeutic interventions have been directed toward impairing the synthesis or accelerating the clearance of Abeta. An equilibrium between blood and brain Abeta exists mediated by carriers that transport Abeta across the blood-brain barrier. Passive immunotherapy has been shown to be effective in mouse models of AD, where the plasma borne antibody binds plasma Abeta causing an efflux of Abeta from the brain. As an alternative to passive immunotherapy we have considered the use of Abeta-degrading peptidases to lower plasma Abeta levels. Here we compare the ability of three Abeta-degrading peptidases to degrade Abeta. Biotinylated peptidases were coupled to the surface of biotinylated erythrocytes via streptavidin. These erythrocyte-bound peptidases degrade Abeta peptide in plasma. Thus, peptidases bound to or expressed on the surface of erythroid cells represent an alternative to passive immunotherapy.
Liu
Yinxing
Y
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, United States.
Guan
Hanjun
H
Beckett
Tina L
TL
Juliano
Maria Aparecida
MA
Juliano
Luiz
L
Song
Eun Suk
ES
Chow
K Martin
KM
Murphy
M Paul
MP
Hersh
Louis B
LB
D000544:Alzheimer Disease / Q000097:blood / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000097:blood / Q000378:metabolism*; D000818:Animals; D019921:Biotinylation; D001812:Blood-Brain Barrier; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007116:Immunization, Passive; D066298:In Vitro Techniques; D007339:Insulysin / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D051379:Mice; D015260:Neprilysin / Q000378:metabolism; D010447:Peptide Hydrolases / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D010447:Peptide Hydrolases; D015260:Neprilysin; D007339:Insulysin; D020781:Matrix Metalloproteinase 1