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Inhibition of α‐synuclein fibril assembly by small molecules: Analysis using epitope‐specific antibodies
Author(s) -
Masuda Masami,
Hasegawa Masato,
aka Takashi,
Oikawa Takayuki,
Yonetani Motokuni,
Yamaguchi Yoshiki,
Kato Koichi,
Hisanaga Shin-ichi,
Goedert Michel
Publication year - 2009
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 - 10.1016/j.febslet.2009.01.037
Subject(s) - fibril , chemistry , epitope , monomer , amyloid (mycology) , small molecule , amyloid fibril , biophysics , biochemistry , antibody , amyloid β , biology , medicine , inorganic chemistry , disease , organic chemistry , pathology , immunology , polymer
The conversion of soluble peptides and proteins into amyloid fibrils and/or intermediate oligomers is believed to be the central event in the pathogenesis of most human neurodegenerative diseases. Existing treatments are at best symptomatic. Accordingly, small molecule inhibitors of amyloid fibril formation and their mechanisms are of great interest. Here we report that the conformational changes undergone by α ‐synuclein as it assembles into amyloid fibrils can be detected by epitope‐specific antibodies. We show that the conformations of polyphenol‐bound α‐synuclein monomers and dimers differ from those of unbound monomers and resemble amyloid fibrils. This strongly suggests that small molecule inhibitors bind and stabilize intermediates of amyloid fibril formation, consistent with the view that inhibitor‐bound molecular species are on‐pathway intermediates.