Oligodendrocyte precursor cells facilitate neuronal lysosome release PMID: 39885146

ADC Targets in Oncology

2026-04-10

Oligodendrocyte precursor cells facilitate neuronal lysosome release

Nat Commun. 2025 Jan 30;16(1):1175. doi: 10.1038/s41467-025-56484-8.

Li-Pao Fang ¹ ² ³ , Ching-Hsin Lin ^# ³ ⁴ , Yasser Medlej ^# ⁵ , Renping Zhao ⁶ , Hsin-Fang Chang ³ ⁴ , Qilin Guo ¹ , Zhonghao Wu ⁷ , Yixun Su ⁷ ⁸ , Na Zhao ¹ ⁹ , Davide Gobbo ¹ , Amanda Wyatt ³ ¹⁰ , Vanessa Wahl ³ ¹⁰ , Frederic Fiore ¹¹ ¹² , Szu-Min Tu ³ ⁴ , Ulrich Boehm ³ ¹⁰ , Wenhui Huang ¹ , Shan Bian ¹³ , Amit Agarwal ¹¹ ¹² , Marcel A Lauterbach ⁵ , Chenju Yi ⁸ , Jianqin Niu ⁷ , Anja Scheller ¹ ³ , Frank Kirchhoff ¹⁴ ¹⁵ , Xianshu Bai ¹⁶ ¹⁷ ¹⁸

Affiliations

1. Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland, 66421, Homburg, Germany.
2. State Key Laboratory of Natural Medicines, Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, 211198, Nanjing, China.
3. Center for Gender-specific Biology and Medicine (CGBM), University of Saarland, 66421, Homburg, Germany.
4. Cellular Neurophysiology, CIPMM, University of Saarland, 66421, Homburg, Germany.
5. Molecular Imaging, CIPMM, University of Saarland, 66421, Homburg, Germany.
6. Biophysics, CIPMM, University of Saarland, 66421, Homburg, Germany.
7. Research Centre, Seventh Affiliated Hospital of Sun Yat-sen University, 518107, Shenzhen, China.
8. Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, 400038, Chongqing, China.
9. Institute of Anatomy and Cell Biology, University of Saarland, 66421, Homburg, Germany.
10. Experimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany.
11. The Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany.
12. Interdisciplinary Center for Neurosciences, Heidelberg University, Heidelberg, Germany.
13. Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
14. Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland, 66421, Homburg, Germany. [email protected].
15. Center for Gender-specific Biology and Medicine (CGBM), University of Saarland, 66421, Homburg, Germany. [email protected].
16. Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland, 66421, Homburg, Germany. [email protected].
17. State Key Laboratory of Natural Medicines, Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, 211198, Nanjing, China. [email protected].
18. Center for Gender-specific Biology and Medicine (CGBM), University of Saarland, 66421, Homburg, Germany. [email protected].
# Contributed equally.

Abstract

Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes. A reduction in the number or branching of OPCs reduces these contacts, which is associated with lysosome accumulation and altered metabolism in neurons and more senescent neurons with age. A similar reduction in OPC branching and neuronal lysosome accumulation is seen in an early-stage mouse model of Alzheimer's disease. Our findings have implications for the prevention of age-related pathologies and the treatment of neurodegenerative diseases.