Amplification of distinct α-synuclein fibril conformers through protein misfolding cyclic amplification

• DOI: 10.1038/emm.2017.1
• Publication Date: 2017-04-07T07:06:32Z
• Authors: Byung Chul Jung; Yoon-Ju Lim; Eun-Jin Bae; Jun Sung Lee; Min Sun Choi; Michael K Lee; He-Jin Lee; Yoon Suk Kim; Seung-Jae Lee
• Keywords: Conformational isomerism; Synucleinopathies; Amyloid (mycology)

Amyloid fibril formation has been implicated in the pathogenesis of neurodegenerative diseases. Fibrillation generates numerous conformers. Presumably, conformers may possess specific biological properties, thus providing a biochemical framework for strains prions. However, precise relationship between various and their pathogenic functions not determined because limited accessibility to adequate amounts fibrils from tissue samples. α-Synuclein is one such protein, it Parkinson disease. Using technique known as protein misfolding cyclic amplification, originally developed amplifying prions, we established procedure through which amplification α-synuclein possible. With trace amount seeds, succeeded fibrils. The replication seeds was faithful terms conformation even after multiple rounds amplification. Moreover, two transgenic mouse each representing distinct synucleinopathy were used investigate different by using this technique. amplified derived extracts these led production with proteinase K digestion profiles. Together, our results demonstrated that could be conformations conserved. This should useful brains body fluids patients afflicted synucleinopathies serve potential diagnostic tool disease other synucleinopathies. A method copy fibrous structures associated diseases aid diagnosis basic research. Specific molecules fold aggregate form deposits amyloid brain cells conditions Alzheimer's Parkinson's Studying misfolded proteins patients' or animal models hampered difficulties obtaining supplies. Seung-Jae Lee colleagues at Seoul National University, co-workers elsewhere Korea USA, have way use small sample "seed" can into larger quantities same disease-linked folding pattern seed. They found Application also explored.