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Transglutaminases Derived from Astrocytes Accelerate Amyloid β Aggregation

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Abstract

Activation of astrocytes has been observed in neurodegenerative diseases including Alzheimer’s disease (AD). Transglutaminase (TG) is a crosslinking enzyme and contributes to cell adhesion, cytoskeleton construct, extracellular matrix formation, and so on. One of the isozymes, tissue-type TG (TG2) is reported to be activated in AD. Moreover, amyloid β1−42 (Aβ), which is aggregated and the aggregation is detected as characteristic pathology in AD brain, is known to be a substrate of TG2. However, contribution and derivation of TGs in brain for Aβ aggregation remain to be clarified. In the present study, we examined the effects of cultured astrocytes prepared from rat embryonic brain cortex on Aβ aggregation. When freshly prepared Aβ was added to cultured astrocytes for 7 days, Aβ monomer decreased and Aβ oligomer unchanged. On the other hand, when Aβ monomer was diluted with astrocytes conditioned medium, Aβ oligomer increased time-dependently, and an inhibitor of TGs, cystamine, blocked it. Furthermore, when cultured astrocytes were stimulated with aggregated Aβ, TG2 expression significantly increased. These results suggest that astrocytes could uptake Aβ monomer to eliminate from brain; however, TGs derived from astrocytes might accelerate Aβ aggregation and the aggregated Aβ might enhance TG2 in astrocytes as a vicious cycle in pathological conditions. Adequate control of TGs expression and function in astrocytes would be an important factor in AD pathology.

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Abbreviations

Aβ:

Amyloid beta

ACM:

Astrocytes conditioned medium

AD:

Alzheimer’s disease

CNS:

Central nervous system

DMEM:

Dulbecco’s modified Eagle medium

FXIII:

Coagulation factor XIII

HRP:

Horseradish peroxidase

iNOS:

Inducible nitric oxide synthase

NF-κB:

Nuclear factor-kappa B

LPS:

Lipopolysaccharide

LRP:

Lipoprotein receptor related protein

RAGE:

Receptor of advanced glycation end product

TG:

Transglutaminase

TLR:

Toll-like receptor

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Acknowledgements

This work was supported in part by JSPS KAKENHI Grant Number JP15J12259 to K.K., JP26850209 to K.T., JP26450447 to M.M., and JP15K07768 to Y.N.

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Authors and Affiliations

  1. Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka, 598-8531, Japan

    Kenji Kawabe, Katsura Takano, Mitsuaki Moriyama & Yoichi Nakamura

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  1. Kenji Kawabe
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  2. Katsura Takano
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  3. Mitsuaki Moriyama
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  4. Yoichi Nakamura
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Correspondence to Katsura Takano.

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Kawabe, K., Takano, K., Moriyama, M. et al. Transglutaminases Derived from Astrocytes Accelerate Amyloid β Aggregation. Neurochem Res 42, 2384–2391 (2017). https://doi.org/10.1007/s11064-017-2258-0

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