Human VCP mutant ALS/FTD microglia display immune and lysosomal phenotypes independently of GPNMB
VCP mutant microglia undergo cell autonomous reactive transformation involving immune and lysosomal dysfunction that partially recapitulate key phenotypes of microglia from other ALS models and post mortem tissue. These phenotypes occur independently of GPNMB. Additionally, VCP mutant microglia elicit non cell autonomous responses in motor neurons and astrocytes involving the JAK-STAT pathway.
Authors
- Pierre Klein (ORCID: https://orcid.org/0000-0002-9209-2939)
- Claudia Ann Smith (ORCID: https://orcid.org/0000-0003-3643-6191)
- Marija Petrić Howe
- Giulia E. Tyzack (ORCID: https://orcid.org/0000-0001-5730-2112)
- Gavin Kelly (ORCID: https://orcid.org/0000-0001-7219-560X)
- Oliver J. Ziff (ORCID: https://orcid.org/0000-0002-1504-7245)
- Cameron A. Hall
- Rickie Patani (ORCID: https://orcid.org/0000-0002-3825-7675)
- Benjamin Clarke (ORCID: https://orcid.org/0000-0001-5775-352X)
- Adel Helmy (ORCID: https://orcid.org/0000-0002-0531-0556)
- Yiran Wang (ORCID: https://orcid.org/0009-0003-0978-5190)
- Michael D. Howell
Institutions
- University of Cambridge (GB)
- The Francis Crick Institute (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- University College London (GB)
Publication Details
- Journal
- Molecular Neurodegeneration
- Published
- 2024-11-26
- DOI
- https://doi.org/10.1186/s13024-024-00773-1
- Citations
- 7
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.73
Funders
- Wellcome Trust
- Francis Crick Institute
- Cancer Research UK
- National Institute for Health and Care Research
- Motor Neurone Disease Association
- Cambridge Trust
- Medical Research Council