2022年5月27日
Actin-binding protein filamin-A drives tau aggregation and contributes to progressive supranuclear palsy pathology.
Science advances
- 巻
- 8
- 号
- 21
- 開始ページ
- eabm5029
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1126/sciadv.abm5029
While amyloid-β lies upstream of tau pathology in Alzheimer's disease, key drivers for other tauopathies, including progressive supranuclear palsy (PSP), are largely unknown. Various tau mutations are known to facilitate tau aggregation, but how the nonmutated tau, which most cases with PSP share, increases its propensity to aggregate in neurons and glial cells has remained elusive. Here, we identified genetic variations and protein abundance of filamin-A in the PSP brains without tau mutations. We provided in vivo biochemical evidence that increased filamin-A levels enhance the phosphorylation and insolubility of tau through interacting actin filaments. In addition, reduction of filamin-A corrected aberrant tau levels in the culture cells from PSP cases. Moreover, transgenic mice carrying human filamin-A recapitulated tau pathology in the neurons. Our data highlight that filamin-A promotes tau aggregation, providing a potential mechanism by which filamin-A contributes to PSP pathology.
- リンク情報
- ID情報
-
- DOI : 10.1126/sciadv.abm5029
- PubMed ID : 35613261
- PubMed Central 記事ID : PMC9132466