microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer’s disease patients
Open accessAbstract
Microglia, the resident immune cells of the brain, are increasingly recognized as key contributors to Alzheimer’s disease (AD) pathology. Multiple studies have identified microRNA-132 (miR-132) as one of the most significantly downregulated microRNAs in AD. Apart from well-established pleiotropic regulatory functions in neurons, previous evidence also suggested a role for miR-132 in regulating (neuro)inflammation. Yet, the precise mechanisms by which miR-132 impacts microglia remain unknown. In this study, we investigated the role of miR-132 in modulating microglial gene expression and function using gain- and loss-of-function approaches in human-induced pluripotent stem cell (iPSC)-derived microglia (iMGs) from both healthy controls and sporadic AD (sAD) patients. Our findings indicate that while miR-132 may not be indispensable for some baseline microglial functions, increasing its expression in sAD iMGs can reverse disease-associated gene expression changes and attenuate inflammatory responses. To further explore its therapeutic potential, we overexpressed miR-132 in hippocampal neurons of an AD mouse model, employing a clinically relevant adeno-associated viral (AAV) delivery method. miR-132 overexpression was well-tolerated and induced non-cell autonomous effects in microglia. This study sheds light into the regulatory role of miR-132 in microglia under both physiological and AD conditions, and emphasizes the importance of optimizing safe dosage parameters for future clinical applications.
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Li, W., Li, X., Wei, Q., Chen, L., Xu, L. P., & Zhou, P. (2023) · Neuroscience · doi:10.1016/j.neuroscience.2023.06.012 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- Salloway SP, Sevingy J, Budur K, Pederson JT, DeMattos RB, Von Rosenstiel P et al (2020) Advancing combination therapy for Alzheimer’s disease. Alzheimer’s, New York, p 6
- Zhang XL, Sun BL, Tian SX, Li L, Zhao YC, Shi PP (2019) MicroRNA-132 reverses cisplatin resistance and metastasis in ovarian cancer by the targeted regulation on Bmi-1. Eur Rev Med Pharmacol Sci 23:3635–3644
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Cited by
Sorted by citations
Maiese, K. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1846280 · Cited by 3 · see citing works
Maiese, K. (2026) · Medical Gas Research · doi:10.4103/mgr.medgasres-d-26-00073 · Cited by 2 · see citing works
Maiese, K. (2026) · Antioxidants · doi:10.3390/antiox15070895 · Cited by 1 · see citing works
Epigenetics in Alzheimer’s disease: from molecular mechanisms to emerging novel biomarkers
D’Aversa, E., Grisafi, M., Pernagallo, S., Salvatori, F., Singh, A. V., Nucciarone, A., Tisato, V., & Gemmati, D. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1959361
Zhou, S., Chen, Y., Yang, X., Xiang, L., Li, B., Qiu, L., Liu, Z., Zhang, T., Liu, F., Zeng, L., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1998588
Maiese, K. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48111163
- Authors
- Penning, A., Snoeck, S., Ormaechea, O. R., Ayyildiz, D., Polzer, O., Buitrago-Arango, M., Capobianco, R., de Winter, F., Balusu, S., Verhaagen, J., Fitzsimons, C. P., d’Ydewalle, C., Lucassen, P. J., Moechars, D., Zhou, L., & Salta, E.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- Janssen (Belgium) (BE)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- University of Amsterdam (NL)
- Corresponding author
- Salta, Evgenia
- ORCID
- Venue
- Acta Neuropathologica Communications
- Published
- 2026-03-07
- Volume
- 14
- Issue
- 1
- ISSN
- 2051-5960 (ISSN-L)
- PMC
- PMC13104464
- OpenAlex
- W7134182450
- Cited by
- 6
- References
- 172
- Citations by year
- 2026: 6
- FWCI
- 14.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Acta Neuropathologica Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion, cc-by)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Health~Holland
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- microRNA-132, Alzheimer's disease, microglia, neuroinflammation, induced pluripotent stem cell-derived microglia, sporadic Alzheimer's disease, microglial gene expression, hippocampal neurons, non-cell-autonomous effects
- MeSH terms
- Aged, Alzheimer Disease, Animals, Cells, Cultured, Disease Models, Animal, Female, Hippocampus, Humans, Inflammation, Male, Mice, Transgenic, Neurons, Microglia, MicroRNAs, Mice, Induced Pluripotent Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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