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Carboxy‐terminal truncations of mouse α‐synuclein alter aggregation and prion‐like seeding
Author(s) -
Sorrentino Zachary A.,
Xia Yuxing,
Gorion KimberlyMarie,
Hass Ethan,
Giasson Benoit I.
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13728
Subject(s) - synucleinopathies , fibril , in vitro , chemistry , microbiology and biotechnology , prion protein , seeding , protein aggregation , amyloid (mycology) , hek 293 cells , in vivo , alpha synuclein , biophysics , biology , biochemistry , disease , genetics , parkinson's disease , gene , pathology , medicine , inorganic chemistry , agronomy
α‐synuclein (αsyn) forms pathologic inclusions in several neurodegenerative diseases termed synucleinopathies. The inclusions are comprised of αsyn fibrils harboring prion‐like properties. Prion‐like activity of αsyn has been studied by intracerebral injection of fibrils into mice, where the presence of a species barrier requires the use of mouse αsyn. Post‐translational modifications to αsyn 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 αsyn found in human disease are recapitulated in mouse αsyn 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 αsyn accelerates aggregation of αsyn but alters prion‐like seeding of inclusion formation.