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Microglial Amyloid-β1-40 Phagocytosis Dysfunction Is Caused by High-Mobility Group Box Protein-1 : Implications for the Pathological Progression of Alzheimer’s Disease
Joint Authors
Saito, Yuki
Shimohama, Shun
Kitamura, Yoshihisa
Takada, Tetsuya
Ashihara, Eishi
Tawa, Manami
Takata, Kazuyuki
Asai, Mayo
Ito, Aina
Tomimoto, Hidekazu
Source
International Journal of Alzheimer's Disease
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-05-08
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
In Alzheimer disease (AD) patient brains, the accumulation of amyloid-β (Aβ) peptides is associated with activated microglia.
Aβ is derived from the amyloid precursor protein; two major forms of Aβ, that is, Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), exist.
We previously reported that rat microglia phagocytose Aβ42, and high mobility group box protein 1 (HMGB1), a chromosomal protein, inhibits phagocytosis.
In the present study, we investigated the effects of exogenous HMGB1 on rat microglial Aβ40 phagocytosis.
In the presence of exogenous HMGB1, Aβ40 markedly increased in microglial cytoplasm, and the reduction of extracellular Aβ40 was inhibited.
During this period, HMGB1 was colocalized with Aβ40 in the cytoplasm.
Furthermore, exogenous HMGB1 inhibited the degradation of Aβ40 induced by the rat microglial cytosolic fraction.
Thus, extracellular HMGB1 may internalize with Aβ40 in the microglial cytoplasm and inhibit Aβ40 degradation by microglia.
This may subsequently delay Aβ40 clearance.
We further confirmed that in AD brains, the parts of senile plaques surrounded by activated microglia are composed of Aβ40, and extracellular HMGB1 is deposited on these plaques.
Taken together, microglial Aβ phagocytosis dysfunction may be caused by HMGB1 that accumulates extracellularly on Aβ plaques, and it may be critically involved in the pathological progression of AD.
American Psychological Association (APA)
Takata, Kazuyuki& Takada, Tetsuya& Ito, Aina& Asai, Mayo& Tawa, Manami& Saito, Yuki…[et al.]. 2012. Microglial Amyloid-β1-40 Phagocytosis Dysfunction Is Caused by High-Mobility Group Box Protein-1 : Implications for the Pathological Progression of Alzheimer’s Disease. International Journal of Alzheimer's Disease،Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-490482
Modern Language Association (MLA)
Takata, Kazuyuki…[et al.]. Microglial Amyloid-β1-40 Phagocytosis Dysfunction Is Caused by High-Mobility Group Box Protein-1 : Implications for the Pathological Progression of Alzheimer’s Disease. International Journal of Alzheimer's Disease No. 2012 (2012), pp.1-11.
https://search.emarefa.net/detail/BIM-490482
American Medical Association (AMA)
Takata, Kazuyuki& Takada, Tetsuya& Ito, Aina& Asai, Mayo& Tawa, Manami& Saito, Yuki…[et al.]. Microglial Amyloid-β1-40 Phagocytosis Dysfunction Is Caused by High-Mobility Group Box Protein-1 : Implications for the Pathological Progression of Alzheimer’s Disease. International Journal of Alzheimer's Disease. 2012. Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-490482
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-490482