Transglutaminases Derived from Astrocytes Accelerate Amyloid β Aggregation

Kenji Kawabe, Katsura Takano, Mitsuaki Moriyama, Yoichi Nakamura

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2384-2391
Number of pages8
JournalNeurochemical Research
Volume42
Issue number8
DOIs
Publication statusPublished - Aug 1 2017
Externally publishedYes

Keywords

  • Amyloid β
  • Astrocyte
  • Cystamine
  • Transglutaminase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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