Aberrant immunomodulatory signature in β-propeller protein-associated neurodegeneration patient iPSC-derived microglia.
Overview
- Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany
- Graduate School of Systemic Neurosciences (GSN), LMU Munich, Munich, Germany
- Neuroproteomics, School of Medicine and Health, TUM University Hospital, Technical University of Munich, Munich, Germany
- German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
- Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- Institute of Biomedical Technologies, National Research Council of Italy, Segrate (Milan), Italy
- Department of Metabolic Biochemistry, Faculty of Medicine, LMU Munich & German Center for Neurodegenerative Diseases (DZNE) Munich, Feodor-Lynen-Strasse 17, D-81377 Munich, Germany
Abstract
Microglia are the brain’s resident immune cells, essential for homeostasis and implicated in common neurodegenerative diseases like Alzheimer’s and Parkinson’s disease (PD), where their early activation and sustained inflammatory mediator release contribute to neuronal loss. However, their role in rare disorders is unclear. β-propeller protein-associated neurodegeneration (BPAN), caused by WDR45 mutations, shares key features with PD, including iron accumulation and dopaminergic neuron loss, but the impact of microglia and mutant WDR45 in BPAN pathophysiology remains unexplored. To address this, we established the first induced pluripotent stem stell (iPSC)-derived microglia model from BPAN patients. Parallel targeted transcriptomic and secretomic profiling revealed a shift from a homeostatic microglial toward a stress-adapted and transcriptionally reprogrammed state characterized by selective remodeling of immune signaling pathways and dysregulation of autophagy and cellular stress responses. Complementary secretomic analysis identified reduced secretion of lysosomal enzymes alongside increased shedding of immune-associated surface proteins, indicating altered lysosomal trafficking and remodeling of microglial immune signaling. These findings identify a distinct microglial phenotype in BPAN and implicate microglial dysfunction as a potential contributor to disease mechanisms, highlighting new avenues for therapeutic strategies targeting neuroimmune pathways.
Supplementary Information: The online version contains supplementary material available at 10.1038/
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- geo:GSE313884, at NCBI GEO; found in “Data availability”
Data availability
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Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 2 keywords, 7 MeSH terms, 1 funder, 82 references.
Cite
This paper
Özata, G., Wise, R. M., Cardona-Alberich, A., Mayeen, N. F., Müller, S. A., Lichtenthaler, S. F., Zecca, L., & Burbulla, L. F. (2026). Aberrant immunomodulatory signature in β-propeller protein-associated neurodegeneration patient iPSC-derived microglia. Scientific reports, 16(1), 18516. https://
BibTeX
@article{ozata2026aberra
author = {Özata, Gamze and Wise, Rachel M and Cardona-Alberich, Aida and Mayeen, Naiyareen F and Müller, Stephan A and Lichtenthaler, Stefan F and Zecca, Luigi and Burbulla, Lena F},
title = {{Aberrant immunomodulatory signature in β-propeller protein-associated neurodegeneration patient iPSC-derived microglia}},
journal = {Scientific reports},
year = {2026},
month = jun,
volume = {16},
number = {1},
pages = {18516},
publisher = {Nature Publishing Group},
issn = {2045-2322},
doi = {10.1038/
url = {https://
pmid = {42297977},
pmcid = {PMC13270018}
}
RIS
TY - JOUR
AU - Özata, Gamze
AU - Wise, Rachel M
AU - Cardona-Alberich, Aida
AU - Mayeen, Naiyareen F
AU - Müller, Stephan A
AU - Lichtenthaler, Stefan F
AU - Zecca, Luigi
AU - Burbulla, Lena F
TI - Aberrant immunomodulatory signature in β-propeller protein-associated neurodegeneration patient iPSC-derived microglia
T2 - Scientific reports
J2 - Sci Rep
PY - 2026
DA - 2026/
VL - 16
IS - 1
SP - 18516
SN - 2045-2322
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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