Statins promote the degradation of extracellular amyloid {beta}-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion.
Statins Promote the Degradation of Extracellular Amyloid β-Peptide by Microglia via Stimulation of Exosome-associated Insulin-degrading Enzyme (IDE) Secretion.pdf
[en] Epidemiological studies indicate that intake of statins decrease the risk of developing Alzheimer disease. Cellular and in vivo studies suggested that statins might decrease the generation of the amyloid β-peptide (Aβ) from the β-amyloid precursor protein. Here, we show that statins potently stimulate the degradation of extracellular Aβ by microglia. The statin-dependent clearance of extracellular Aβ is mainly exerted by insulin-degrading enzyme (IDE) that is secreted in a nonconventional pathway in association with exosomes. Stimulated IDE secretion and Aβ degradation were also observed in blood of mice upon peripheral treatment with lovastatin. Importantly, increased IDE secretion upon lovastatin treatment was dependent on protein isoprenylation and up-regulation of exosome secretion by fusion of multivesicular bodies with the plasma membrane. These data demonstrate a novel pathway for the nonconventional secretion of IDE via exosomes. The modulation of this pathway could provide a new strategy to enhance the extracellular clearance of Aβ.
Disciplines :
Neurology
Author, co-author :
Tamboli, Irfan Y; Departments of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany
Barth, Esther; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Christian, Leonie; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Siepmann, Martin; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Kumar, Sathish; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Singh, Sandesh; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Tolksdorf, Karen; Department of Neurology, University of Bonn, 53127 Bonn, Germany
HENEKA, Michael ; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Lütjohann, Dieter; Department of Clinical Pharmacology and Biochemistry, University of Bonn, 53127 Bonn, Germany
Wunderlich, Patrick; Department of Neurology, University of Bonn, 53127 Bonn, Germany
Walter, Jochen; Department of Neurology, University of Bonn, 53127 Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Statins promote the degradation of extracellular amyloid {beta}-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion.
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