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

Abstract

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 invitro, 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.