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Cited by 108Alzheimer's disease research and treatmentsComputational Drug Discovery MethodsCholinesterase and Neurodegenerative Diseases

Drug repositioning for Alzheimer’s disease based on systematic “omics” data mining

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Zhang, Ming, Schmitt-Ulms, Gerold, Sato, Christine, Xi, Zhengrui, Zhang, Yalun, Zhou, Ye, St George-Hyslop, Peter, Rogaeva, Ekaterina·2016·PLOS ONE
DOI 10.1371/journal.pone.0168812PMC PMC5179106
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Abstract

Traditional drug development for Alzheimer's disease (AD) is costly, time consuming and burdened by a very low success rate. An alternative strategy is drug repositioning, redirecting existing drugs for another disease. The large amount of biological data accumulated to date warrants a comprehensive investigation to better understand AD pathogenesis and facilitate the process of anti-AD drug repositioning. Hence, we generated a list of anti-AD protein targets by analyzing the most recent publically available 'omics' data, including genomics, epigenomics, proteomics and metabolomics data. The information related to AD pathogenesis was obtained from the OMIM and PubMed databases. Drug-target data was extracted from the DrugBank and Therapeutic Target Database. We generated a list of 524 AD-related proteins, 18 of which are targets for 75 existing drugs-novel candidates for repurposing as anti-AD treatments. We developed a ranking algorithm to prioritize the anti-AD targets, which revealed CD33 and MIF as the strongest candidates with seven existing drugs. We also found 7 drugs inhibiting a known anti-AD target (acetylcholinesterase) that may be repurposed for treating the cognitive symptoms of AD. The CAD protein and 8 proteins implicated by two 'omics' approaches (ABCA7, APOE, BIN1, PICALM, CELF1, INPP5D, SPON1, and SOD3) might also be promising targets for anti-AD drug development. Our systematic 'omics' mining suggested drugs with novel anti-AD indications, including drugs modulating the immune system or reducing neuroinflammation that are particularly promising for AD intervention. Furthermore, the list of 524 AD-related proteins could be useful not only as potential anti-AD targets but also considered for AD biomarker development.

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  • Demecarium was first suggested as an AD repurposing candidate in 2014, with subsequent support in two studies; after 2016, the drug was not mentioned again.

    “demecarium was first suggested as an AD repurposing candidate in 2014 (Croset et al., 2014), with subsequent support in two studies (Jamal et al., 2015;Zhang et al., 2016); however, after 2016, the drug was not mentioned again.”

    From Drug repurposing for Alzheimer’s disease from 2012–2022—a 10-year literature review (2023) · cites this paper as Zhang et al., 2016

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Cited by

Sorted by citations

Authors
Zhang, M., Schmitt-Ulms, G., Sato, C., Xi, Z., Zhang, Y., Zhou, Y., St George-Hyslop, P., & Rogaeva, E.
Affiliations
University of Toronto (CA)
Corresponding author
Zhang, Ming
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2016-12-22
Volume
11
Issue
12
Pages
e0168812
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0168812
PMC
PMC5179106
OpenAlex
W2565611518
Cited by
108
References
10
Citations by year
2026: 1 · 2025: 3 · 2024: 15 · 2023: 11 · 2022: 18 · 2021: 16 · 2020: 18 · 2019: 11 · 2018: 12 · 2017: 3
FWCI
6.98
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Wellcome Trust
  • Medical Research Council
  • Ontario Research Fund
  • Canadian Institutes of Health Research
  • National Institute of Health Research Cambridge Biomedical Research Unit in Dementia
  • National Institutes of Health
  • Alzheimer Society of Ontario
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
Alzheimer's disease, drug repurposing, Alzheimer's disease pathogenesis, CD33, macrophage migration inhibitory factor, acetylcholinesterase inhibitors, neuroinflammation, immunomodulation, Alzheimer's disease biomarkers, apolipoprotein E, ABCA7, BIN1, PICALM, CELF1, INPP5D, SPON1, SOD3
MeSH terms
Alzheimer Disease, Humans, Biomarkers, Databases, Factual, Genomics, Proteomics, Metabolomics, Data Mining, Drug Repositioning

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