Informace o projektu
Pathogenic SORL1 variants in Alzheimer’s disease
(SORLA - FIX)
- Kód projektu
- 8F20009
- Období řešení
- 7/2020 - 12/2024
- Investor / Programový rámec / typ projektu
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Ministerstvo školství, mládeže a tělovýchovy ČR
- Společné programování
- Neurodegenerativní onemocnění (JPND)
- Fakulta / Pracoviště MU
- Lékařská fakulta
- Spolupracující organizace
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Aarhus Universitet
Amsterdam UMC, locatie VUmc
Max-Planck Institute of Biophysics
The SORLA protein is a neuronal sorting receptor encoded by the SORL1 gene. Functional SORLA keeps the levels of Amyloid-β in the brain in a healthy balance regulating APP processing into Amyloid-β, and by binding excess Amyloid-β to target it for lysosomal degradation. In the past two-three years it has become clear that heterozygous, damaging variants in the SORL1 gene are associated with and possibly causative for AD. Furthermore, the load of pathogenic and risk-increasing SORL1 variants in AD patients is large, which suggests that it is imperative to invest in the identification of those at risk to become affected with SORL1-associated AD, and the selective treatment of affected individuals. In this proposal we have created a collaboration of international investigators who are highly capable of answering the open questions regarding SORL1 variant pathogenicity and protein functions. Within this synergy of expertise, we will generate a working-pipeline to assess SORL1 variant pathogenicity, allowing the accurate diagnosis of patients with SORL1-associated AD and we will invest in the identification of selective SORL1-boosting or SORL1-fixing treatments applicable to individuals affected by compromised SORLA function.
Cíle udržitelného rozvoje
Masarykova univerzita se hlásí k cílům udržitelného rozvoje OSN, jejichž záměrem je do roku 2030 zlepšit podmínky a kvalitu života na naší planetě.
Publikace
Počet publikací: 4
2024
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The SORL1 p.Y1816C variant causes impaired endosomal dimerization and autosomal dominant Alzheimer's disease
Proceedings of the National Academy of Sciences of the United States of America, rok: 2024, ročník: 121, vydání: 37, DOI
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VISUALIZATION OF THE SORLA PROTEIN MUTATIONS IN THE ALZHEIMER’S DISEASE DEVELOPMENT
Rok: 2024, druh: Konferenční abstrakty
2023
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Cerebral organoids derived from patients with Alzheimer´s disease with PSEN1/2 mutations have defective tissue patterning and altered development
CELL REPORTS, rok: 2023, ročník: 42, vydání: 11, DOI
2022
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Human iPSC-Derived Neural Models for Studying Alzheimer’s Disease: from Neural Stem Cells to Cerebral Organoids
Stem Cell Reviews and Reports, rok: 2022, ročník: 18, vydání: 2, DOI