Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype
Overall, our results suggest that inflammation-induced metabolic reprogramming places lysosomes under substantial stress. Lysosomal stress is more detrimental in APOE4/4 microglia, which exhibit endo-lysosomal defects.
Authors
- Marianna Hellén
- Mari Takalo (ORCID: https://orcid.org/0000-0002-6609-1860)
- Michael Peitz (ORCID: https://orcid.org/0000-0001-5777-4240)
- Marja Koskuvi (ORCID: https://orcid.org/0000-0002-1646-9992)
- Pinja Kettunen (ORCID: https://orcid.org/0000-0002-3119-4499)
- Alfredo Ramı́rez (ORCID: https://orcid.org/0000-0003-4991-763X)
- Ville Leinonen (ORCID: https://orcid.org/0000-0002-4282-4687)
- Klaus Fließbach (ORCID: https://orcid.org/0000-0002-0183-7510)
- Taisia Rõlova (ORCID: https://orcid.org/0000-0002-8869-593X)
- Olli K. Kärkkäinen (ORCID: https://orcid.org/0000-0003-0825-4956)
- Jari Koıstınaho (ORCID: https://orcid.org/0000-0001-6559-1153)
- Stefan F. Lichtenthaler (ORCID: https://orcid.org/0000-0003-2211-2575)
- Šárka Lehtonen (ORCID: https://orcid.org/0000-0002-5055-9414)
- Stephan A. Müller (ORCID: https://orcid.org/0000-0003-3414-307X)
- Noora Räsänen (ORCID: https://orcid.org/0000-0003-4521-4398)
- Isabelle Weert (ORCID: https://orcid.org/0000-0002-2888-478X)
- Mikko Hiltunen
Institutions
- University of Helsinki (FI)
- University of Bonn (DE)
- The University of Texas at San Antonio Health Science Center (US)
- University of Eastern Finland (FI)
- University of Cologne (DE)
- University Hospital Bonn (DE)
- German Center for Neurodegenerative Diseases (DE)
- TUM Klinikum (DE)
- Kuopio University Hospital (FI)
- Institute for Neurodegenerative Disorders (US)
- Munich Cluster for Systems Neurology (DE)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Delfin Technologies (Finland) (FI)
- Technical University of Munich (DE)
Publication Details
- Journal
- Journal of Neuroinflammation
- Published
- 2025-06-02
- DOI
- https://doi.org/10.1186/s12974-025-03470-y
- Citations
- 9
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 12.19
Funders
- Itä-Suomen Yliopisto
- Helsingin Yliopisto
- Biocenter Finland
- Helsinki Institute of Life Science, Helsingin Yliopisto