The DOI matches its Crossref record; 94 of the 94 references it cites were found in a registry or an index.
Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow
Open accessAbstract
A reduced removal of dysfunctional mitochondria is common to aging and age-related neurodegenerative pathologies such as Alzheimer’s disease (AD). Strategies for treating such impaired mitophagy would benefit from the identification of mitophagy modulators. Here we report the combined use of unsupervised machine learning (involving vector representations of molecular structures, pharmacophore fingerprinting and conformer fingerprinting) and a cross-species approach for the screening and experimental validation of new mitophagy-inducing compounds. From a library of naturally occurring compounds, the workflow allowed us to identify 18 small molecules, and among them two potent mitophagy inducers (Kaempferol and Rhapontigenin). In nematode and rodent models of AD, we show that both mitophagy inducers increased the survival and functionality of glutamatergic and cholinergic neurons, abrogated amyloid-β and tau pathologies, and improved the animals’ memory. Our findings suggest the existence of a conserved mechanism of memory loss across the AD models, this mechanism being mediated by defective mitophagy. The computational–experimental screening and validation workflow might help uncover potent mitophagy modulators that stimulate neuronal health and brain homeostasis.
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Cites
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Cited by
Mitophagy in human health, ageing and disease
Picca, A., Faitg, J., Auwerx, J., Ferrucci, L., & D’Amico, D. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00930-8 · Cited by 635
New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary
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Self-citationMitophagy in Alzheimer’s disease: Molecular defects and therapeutic approaches
Mary, A., Eysert, F., Checler, F., & Chami, M. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01631-6 · Cited by 244
“Kaempferol and Rhapontigenin restored memory deficits in both Tau and Aβ AD study models [91].”
InfluentialUrolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions
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Metadata
- Authors
- Xie, C., Zhuang, X.-X., Niu, Z., Ai, R., Lautrup, S., Zheng, S., Jiang, Y., Han, R., Gupta, T. S., Cao, S., Lagartos-Donate, M. J., Cai, C.-Z., Xie, L.-M., Caponio, D., Wang, W.-W., Schmauck-Medina, T., Zhang, J., Wang, H.-L., Lou, G., Xiao, X., Zheng, W., Palikaras, K., Yang, G., Caldwell, K. A., Caldwell, G. A., Shen, H.-M., Nilsen, H., Lu, J.-H., & Fang, E. F.
- Venue
- Nature Biomedical Engineering
- Published
- 2022-01-06
- Volume
- 6
- Issue
- 1
- Pages
- 76-93
- ISSN
- 2157-846X (ISSN-L)
- OpenAlex
- W4205241347
- Cited by
- 336
- References
- 94
- FWCI
- 37.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Xie, C., Zhuang, X.-X., Niu, Z., Ai, R., Lautrup, S., Zheng, S., Jiang, Y., Han, R., Gupta, T. S., Cao, S., Lagartos-Donate, M. J., Cai, C.-Z., Xie, L.-M., Caponio, D., Wang, W.-W., Schmauck-Medina, T., Zhang, J., Wang, H.-L., Lou, G., . . . Fang, E. F. (2022). Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-021-00819-5
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
