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DYRK1A Inhibitors and Perspectives for the Treatment of Alzheimer's Disease
de Souza MM, Cenci AR, Teixeira KF, Machado V, Mendes Schuler MCG, Gonçalves AE, Paula Dalmagro A, André Cazarin C et al.. Current medicinal chemistry, 2023-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most common form of dementia, especially in the elderly. Due to the increase in life expectancy, in recent years, there has been an excessive growth in the number of people affected by this disease, causing serious problems for health systems. In recent years, research has been intensified to find new therapeutic approaches that prevent the progression of the disease. In this sense, recent studies indicate that the dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) gene, which is located on chromosome 21q22.2 and overexpressed in Down syndrome (DS), may play a significant role in developmental brain disorders and early onset neurodegeneration, neuronal loss and dementia in DS and AD. Inhibiting DYRK1A may serve to stop the phenotypic effects of its overexpression and, therefore, is a potential treatment strategy for the prevention of ageassociated neurodegeneration, including Alzheimer-type pathology. Objective In this review, we investigate the contribution of DYRK1A inhibitors as potential anti-AD agents. Methods A search in the literature to compile an in vitro dataset including IC50 values involving DYRK1A was performed from 2014 to the present day. In addition, we carried out structure-activity relationship studies based on in vitro and in silico data. Results molecular modeling and enzyme kinetics studies indicate that DYRK1A may contribute to AD pathology through its proteolytic process, reducing its kinase specificity. Conclusion further evaluation of DYRK1A inhibitors may contribute to new therapeutic approaches for AD.
Key findings
- In this sense, recent studies indicate that the dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) gene, which is located on chromosome 21q22.2 and overexpressed in Down syndrome (DS), may play a significant role in developmental brain disorders and early onset neurodegeneration, neuronal loss and dementia in DS and AD.
- Results molecular modeling and enzyme kinetics studies indicate that DYRK1A may contribute to AD pathology through its proteolytic process, reducing its kinase specificity.
Why it matters
This review examines whether drugs that inhibit the DYRK1A enzyme could be a treatment strategy for Alzheimer's disease, since the gene is overexpressed in Down syndrome and may contribute to neurodegeneration. The evidence comes from laboratory and computer studies, so this is early-stage research and no clinical trial results are reported.
Study details
- Evidence strengthLow
How this study scored 40/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Current medicinal chemistry) |
| Journal's citation record | 2 / 4 | Current Medicinal Chemistry: journal h-index 229 (OpenAlex, 2026-10-29) |
| 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 | 3 / 5 | 2023 — within 6 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 | 3 / 7 | Cited 27 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.4 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 2 / 6 | Cited 2.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 20 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Adriano Defini Andricopulo: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Universidade de São Paulo: institution h-index 936 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35726411) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
de Souza, M. M., Cenci, A. R., Teixeira, K. F., Machado, V., Mendes Schuler, M. C. G., Gonçalves, A. E., et al. (2023). DYRK1A Inhibitors and Perspectives for the Treatment of Alzheimer's Disease. Current medicinal chemistry. https://doi.org/10.2174/0929867329666220620162018
Vancouver
de Souza MM, Cenci AR, Teixeira KF, Machado V, Mendes Schuler MCG, Gonçalves AE, et al. DYRK1A Inhibitors and Perspectives for the Treatment of Alzheimer's Disease. Current medicinal chemistry. 2023. doi:10.2174/0929867329666220620162018. PMID: 35726411.
BibTeX
@article{desouza2023-35726411,
author = {de Souza, M. M. and Cenci, A. R. and Teixeira, K. F. and Machado, V. and Mendes Schuler, M. C. G. and Gonçalves, A. E. and Paula Dalmagro, A. and André Cazarin, C. and others},
title = {{DYRK1A Inhibitors and Perspectives for the Treatment of Alzheimer's Disease}},
journal = {Current medicinal chemistry},
year = {2023},
doi = {10.2174/0929867329666220620162018},
pmid = {35726411},
url = {https://doi.org/10.2174/0929867329666220620162018}
}
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