Carboxy-terminal truncations of mouse α-synuclein alter aggregation and prion-like seeding

FEBS Letters

article

Zachary A. Sorrentino¹  Yuxing Xia¹  Kimberly-Marie Gorion¹  Ethan Hass¹  Benoit I. Giasson¹ 

[1] Department of Neuroscience, College of Medicine, University of Florida;Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida;McKnight Brain Institute, College of Medicine, University of Florida

关键词: amyloid;    fibril;    inclusion formation;    Parkinson’s disease;    prion;    seeding;    truncation;    a-synuclein;   

DOI  :  10.1002/1873-3468.13728

来源: John Wiley & Sons Ltd.

【 摘 要 】

a-synuclein (asyn) forms pathologic inclusions in several neurodegenerative diseases termed synucleinopathies. The inclusions are comprised of asyn fibrils harboring prion-like properties. Prion-like activity of asyn has been studied by intracerebral injection of fibrils into mice, where the presence of a species barrier requires the use of mouse asyn. Post-translational modifications to asyn such as carboxy (C)-terminal truncation occur in synucleinopathies, and their implications for prion-like aggregation and seeding are under investigation. Herein, C-truncated forms of asyn found in human disease are recapitulated in mouse asyn to study their seeding activity in vitro, in HEK293T cells, in neuronal–glial culture, and in nontransgenic mice. The results show that C-truncation of mouse asyn accelerates aggregation of asyn but alters prion-like seeding of inclusion formation.

【 授权许可】

Unknown