Engineered peroxisomes and patient-derived iPSC models as potential biomaterial platforms for precision neuroprotection in oxidative stress-driven central nervous system disorders
5 affiliations
- 1Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- 2Smart Convergence Materials Analysis Center, Wonkwang University, Iksan, Republic of Korea
- 3Integrated Omics Institute, Wonkwang University, Iksan, Republic of Korea
- 4BioTalentum Ltd., Godollo, Hungary
- 5Department of Biomedical Materials Science, Graduate School of JABA, Wonkwang University, Iksan, Republic of Korea
Abstract
Peroxisomes couple hydrogen peroxide metabolism to lipid homeostasis, making their functions relevant to neurological disease and to the design of intracellular catalytic biomaterials. However, the strength of disease-specific evidence and the functions reproduced by current materials vary substantially. This narrative review distinguishes modified biological peroxisomes from artificial and biomimetic platforms and evaluates how patient-derived induced pluripotent stem cell (iPSC) models could support their development. We examine membrane chemistry, substrate permeability, enzyme retention, catalytic activity, cell targeting, blood-brain barrier transport, three-dimensional tissue penetration, and intracellular fate. We separate the established causal role of peroxisomal defects in primary peroxisomal disorders from associative or unresolved findings in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Kleefstra syndrome is discussed as a hypothesis-generating neurodevelopmental model, without assuming a primary peroxisomal defect. Published artificial-organelle studies establish selected catalytic and delivery capabilities, but do not validate the integrated patient-specific CNS therapeutic strategy proposed here. We therefore outline a staged evaluation framework that combines materials characterization with mechanistic controls, differentiated neural cultures, multicellular models, animal pharmacology, safety, and manufacturing assessment. Comparison with conventional antioxidant carriers, plasmalogen supplementation, and PPAR agonists should determine whether compartmentalized catalysis offers a measurable advantage. We provide a platform classification, a disease-resolved evidence hierarchy, and a set of controls and measurable endpoints intended to make peroxisome-inspired constructs comparable across studies. Clinical development will require evidence of disease-relevant benefit beyond ROS reduction and an acceptable therapeutic window.
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BibTeX
@article{matta2026engineered,
title = {{Engineered peroxisomes and patient-derived iPSC models as potential biomaterial platforms for precision neuroprotection in oxidative stress-driven central nervous system disorders}},
author = {Csaba Matta and Yoon-Hee Cheon and Judit Vágó and Zoltán Mészár and Ee-Hyun Kim and Songling Jiang and Andrea Balogh and Melinda Zana and András Dinnyés and Eun-Jung Jin},
journal = {Materials today. Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103752},
url = {https://europepmc.org/article/PMC/PMC13717160},
note = {CC BY},
}
RIS
TY - JOUR
TI - Engineered peroxisomes and patient-derived iPSC models as potential biomaterial platforms for precision neuroprotection in oxidative stress-driven central nervous system disorders
AU - Csaba Matta
AU - Yoon-Hee Cheon
AU - Judit Vágó
AU - Zoltán Mészár
AU - Ee-Hyun Kim
AU - Songling Jiang
AU - Andrea Balogh
AU - Melinda Zana
AU - András Dinnyés
AU - Eun-Jung Jin
PY - 2026
DA - 2026/10/13
JO - Materials today. Bio
DO - 10.1016/j.mtbio.2026.103752
UR - https://europepmc.org/article/PMC/PMC13717160
AB - Peroxisomes couple hydrogen peroxide metabolism to lipid homeostasis, making their functions relevant to neurological disease and to the design of intracellular catalytic biomaterials. However, the strength of disease-specific evidence and the functions reproduced by current materials vary substantially. This narrative review distinguishes modified biological peroxisomes from artificial and biomimetic platforms and evaluates how patient-derived induced pluripotent stem cell (iPSC) models could support their development. We examine membrane chemistry, substrate permeability, enzyme retention, catalytic activity, cell targeting, blood-brain barrier transport, three-dimensional tissue penetration, and intracellular fate. We separate the established causal role of peroxisomal defects in primary peroxisomal disorders from associative or unresolved findings in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Kleefstra syndrome is discussed as a hypothesis-generating neurodevelopmental model, without assuming a primary peroxisomal defect. Published artificial-organelle studies establish selected catalytic and delivery capabilities, but do not validate the integrated patient-specific CNS therapeutic strategy proposed here. We therefore outline a staged evaluation framework that combines materials characterization with mechanistic controls, differentiated neural cultures, multicellular models, animal pharmacology, safety, and manufacturing assessment. Comparison with conventional antioxidant carriers, plasmalogen supplementation, and PPAR agonists should determine whether compartmentalized catalysis offers a measurable advantage. We provide a platform classification, a disease-resolved evidence hierarchy, and a set of controls and measurable endpoints intended to make peroxisome-inspired constructs comparable across studies. Clinical development will require evidence of disease-relevant benefit beyond ROS reduction and an acceptable therapeutic window.
SN - 2590-0064
ER -