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Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain.
Life Sci. All. 6:e202201730 (2023)
In age-related neurodegenerative diseases, like Alzheimer's and Parkinson's, disease-specific proteins become aggregation-prone and form amyloid-like deposits. Depletion of SERF proteins ameliorates this toxic process in worm and human cell models for diseases. Whether SERF modifies amyloid pathology in mammalian brain, however, has remained unknown. Here, we generated conditional Serf2 knockout mice and found that full-body deletion of Serf2 delayed embryonic development, causing premature birth and perinatal lethality. Brain-specific Serf2 knockout mice, on the other hand, were viable, and showed no major behavioral or cognitive abnormalities. In a mouse model for amyloid-β aggregation, brain depletion of Serf2 altered the binding of structure-specific amyloid dyes, previously used to distinguish amyloid polymorphisms in the human brain. These results suggest that Serf2 depletion changed the structure of amyloid deposits, which was further supported by scanning transmission electron microscopy, but further study will be required to confirm this observation. Altogether, our data reveal the pleiotropic functions of SERF2 in embryonic development and in the brain and support the existence of modifying factors of amyloid deposition in mammalian brain, which offer possibilities for polymorphism-based interventions.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Alpha-synuclein Aggregation; Onset Alzheimers-disease; Parkinsons-disease; Precursor Protein; Beta Fibrils; Cell-cycle; In-vitro; Mutation; Platform; Tau
ISSN (print) / ISBN
2575-1077
e-ISSN
2575-1077
Journal
Life Science Alliance
Quellenangaben
Volume: 6,
Issue: 7,
Article Number: e202201730
Publisher
EMBO Press
Publishing Place
Heidelberg
Non-patent literature
Publications
Reviewing status
Peer reviewed
Grants
German Federal Ministry of Education and Research
CORBEL
Alumni chapter Gooische Groningers
European Research Council (ERC) starting grant
Meervoud Grant from NWO
NWO National Roadmap for Large-Scale Research Infrastructure of the Dutch Research Council
STW
NWO
ZonMw
CORBEL
Alumni chapter Gooische Groningers
European Research Council (ERC) starting grant
Meervoud Grant from NWO
NWO National Roadmap for Large-Scale Research Infrastructure of the Dutch Research Council
STW
NWO
ZonMw