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Heckmann, Bradlee L., Teubner, Brett J. W., Boada-Romero, Emilio, Tummers, Bart, Guy, Clifford, Fitzgerald, Patrick, Mayer, Ulrike 
ORCID: https://orcid.org/0000-0003-2328-0052, Carding, Simon, Zakharenko, Stanislav S., Wileman, Thomas and Green, Douglas R.
(2020)
Noncanonical function of an autophagy protein prevents spontaneous Alzheimer’s disease.
Science Advances, 6 (33).
eabb9036.
ISSN 2375-2548
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Abstract
Noncanonical functions of autophagy proteins have been implicated in neurodegenerative conditions, including Alzheimer’s disease (AD). The WD domain of the autophagy protein Atg16L is dispensable for canonical autophagy but required for its noncanonical functions. Two-year-old mice lacking this domain presented with robust β-amyloid (Aβ) pathology, tau hyperphosphorylation, reactive microgliosis, pervasive neurodegeneration, and severe behavioral and memory deficiencies, consistent with human disease. Mechanistically, we found this WD domain was required for the recycling of Aβ receptors in primary microglia. Pharmacologic suppression of neuroinflammation reversed established memory impairment and markers of disease pathology in this novel AD model. Therefore, loss of the Atg16L WD domain drives spontaneous AD in mice, and inhibition of neuroinflammation is a potential therapeutic approach for treating neurodegeneration and memory loss. A decline in expression of ATG16L in the brains of human patients with AD suggests the possibility that a similar mechanism may contribute in human disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being |
| Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 27 Aug 2020 00:00 |
| Last Modified: | 06 Jun 2024 15:12 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/76668 |
| DOI: | 10.1126/sciadv.abb9036 |
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