| Autor: |
M, Rodrigues, P, Bhattacharjee, A, Brinkmalm, D T, Do, C M, Pearson, S, De, A, Ponjavic, J A, Varela, K, Kulenkampff, I, Baudrexel, D, Emin, F S, Ruggeri, J E, Lee, A R, Carr, T P J, Knowles, H, Zetterberg, T N, Snaddon, S, Gandhi, S F, Lee, D, Klenerman |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Nature chemistry. 14(9) |
| ISSN: |
1755-4349 |
| Popis: |
The composition of soluble toxic protein aggregates formed in vivo is currently unknown in neurodegenerative diseases, due to their ultra-low concentration in human biofluids and their high degree of heterogeneity. Here we report a method to capture amyloid-containing aggregates in human biofluids in an unbiased way, a process we name amyloid precipitation. We use a structure-specific chemical dimer, a Y-shaped, bio-inspired small molecule with two capture groups, for amyloid precipitation to increase affinity. Our capture molecule for amyloid precipitation (CAP-1) consists of a derivative of Pittsburgh Compound B (dimer) to target the cross β-sheets of amyloids and a biotin moiety for surface immobilization. By coupling CAP-1 to magnetic beads, we demonstrate that we can target the amyloid structure of all protein aggregates present in human cerebrospinal fluid, isolate them for analysis and then characterize them using single-molecule fluorescence imaging and mass spectrometry. Amyloid precipitation enables unbiased determination of the molecular composition and structural features of the in vivo aggregates formed in neurodegenerative diseases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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