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Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease
Habchi J, Chia S, Limbocker R, Mannini B, Ahn M, Perni M, Hansson O, Arosio P et al.. Proceedings of the National Academy of Sciences of the United States of America, 2016-12-23
Topic: Amyloid, tau and blood-test diagnosis
The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer's disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery.
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APA 7th
Habchi, J., Chia, S., Limbocker, R., Mannini, B., Ahn, M., Perni, M., et al. (2017). Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1615613114
Vancouver
Habchi J, Chia S, Limbocker R, Mannini B, Ahn M, Perni M, et al. Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America. 2017. doi:10.1073/pnas.1615613114. PMID: 28011763.
BibTeX
@article{habchi2017-28011763,
author = {Habchi, J. and Chia, S. and Limbocker, R. and Mannini, B. and Ahn, M. and Perni, M. and Hansson, O. and Arosio, P. and others},
title = {{Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2017},
doi = {10.1073/pnas.1615613114},
pmid = {28011763},
url = {https://doi.org/10.1073/pnas.1615613114}
}
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Key findings
- Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28011763) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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