Polycation-induced oligomerization and accelerated fibrillation of human alpha-synuclein in vitro.
The aggregation and fibrillation of alpha-synuclein has been implicated as a causative factor in Parkinson's disease and several other neurodegenerative disorders known as synucleinopathies. The effect of different factors on the process of fibril formation has been intensively studied in vitro. We show here that alpha-synuclein interacts with different unstructured polycations (spermine, polylysine, polyarginine, and polyethyleneimine) to form specific complexes. In addition, the polycations catalyze alpha-synuclein oligomerization. The formation of alpha-synuclein-polycation complexes was not accompanied by significant structural changes in alpha-synuclein. However, alpha-synuclein fibrillation was dramatically accelerated in the presence of polycations. The magnitude of the accelerating effect depended on the nature of the polymer, its length, and concentration. The results illustrate the potential critical role of electrostatic interactions in protein aggregation, and the potential role of naturally occurring polycations in modulating alpha-synuclein aggregation.
Goers
John
J
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
Uversky
Vladimir N
VN
Fink
Anthony L
AL
D002942:Circular Dichroism; D006801:Humans; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000648:ultrastructure; D011073:Polyamines / Q000378:metabolism*; D000071228:Polyelectrolytes; D011108:Polymers / Q000378:metabolism*; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D011073:Polyamines; D000071228:Polyelectrolytes; D011108:Polymers; D051843:Synucleins; D051844:alpha-Synuclein; C497604:SNCA protein, human