Abstract
Aside from being an integral protein involved in the synthesis and hydrolysis of ATP, Ecto-F1-ATPase plays a role in cholesterol homeostasis. We demonstrated the presence of autoantibodies to ecto-F1-ATPase (ASabs) in sera and cerebrospinal fluids from patients with Alzheimer's disease (AD). Herein we show that ASabs, unlike irrelevant antibodies, can increase cellular uptake of HDL, a risk factor for the development of AD, via a mechanism involving the prototypical function of ecto-F1-ATPase: the generation of ADP due to the hydrolysis of ATP. Piceatannol, a specific inhibitor ecto-F1-ATPase, completely hindered these effects. We hypothesize that ASabs could exert a pathogenetic role in AD.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenosine Diphosphate / metabolism
-
Adenosine Triphosphate / metabolism
-
Aged
-
Aged, 80 and over
-
Alzheimer Disease / enzymology*
-
Alzheimer Disease / immunology
-
Antibody Specificity
-
Apoptosis / drug effects
-
Autoantibodies / immunology
-
Autoantibodies / pharmacology*
-
Cell Line
-
Cholesterol, HDL / metabolism*
-
Enzyme Inhibitors / pharmacology
-
Extracellular Space / metabolism
-
Female
-
Fluorescent Dyes
-
Humans
-
Male
-
Middle Aged
-
Proton-Translocating ATPases / antagonists & inhibitors*
-
Proton-Translocating ATPases / cerebrospinal fluid
-
Proton-Translocating ATPases / immunology*
-
Stilbenes / pharmacology
Substances
-
Autoantibodies
-
Cholesterol, HDL
-
Enzyme Inhibitors
-
Fluorescent Dyes
-
Stilbenes
-
Adenosine Diphosphate
-
3,3',4,5'-tetrahydroxystilbene
-
Adenosine Triphosphate
-
Proton-Translocating ATPases