論文

査読有り 国際誌
2019年6月1日

Sequence- and seed-structure-dependent polymorphic fibrils of alpha-synuclein.

Biochimica et biophysica acta. Molecular basis of disease
  • Goki Tanaka
  • ,
  • Tomoyuki Yamanaka
  • ,
  • Yoshiaki Furukawa
  • ,
  • Naoko Kajimura
  • ,
  • Kaoru Mitsuoka
  • ,
  • Nobuyuki Nukina

1865
6
開始ページ
1410
終了ページ
1420
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbadis.2019.02.013

Synucleinopathies comprise a diverse group of neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies, and multiple system atrophy. These share a common pathological feature, the deposition of alpha-synuclein (a-syn) in neurons or oligodendroglia. A-syn is highly conserved in vertebrates, but the primary sequence of mouse a-syn differs from that of human at seven positions. However, structural differences of their aggregates remain to be fully characterized. In this study, we found that human and mouse a-syn aggregated in vitro formed morphologically distinct amyloid fibrils exhibiting twisted and straight structures, respectively. Furthermore, we identified different protease-resistant core regions, long and short, in human and mouse a-syn aggregates. Interestingly, among the seven unconserved amino acids, only A53T substitution, one of the familial PD mutations, was responsible for structural conversion to the straight-type. Finally, we checked whether the structural differences are transmissible by seeding and found that human a-syn seeded with A53T aggregates formed straight-type fibrils with short protease-resistant cores. These results suggest that a-syn aggregates form sequence-dependent polymorphic fibrils upon spontaneous aggregation but become seed structure-dependent upon seeding.

リンク情報
DOI
https://doi.org/10.1016/j.bbadis.2019.02.013
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30790619
ID情報
  • DOI : 10.1016/j.bbadis.2019.02.013
  • ISSN : 0925-4439
  • PubMed ID : 30790619

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