ArticleScience advances2020
Noncanonical function of an autophagy protein prevents spontaneous Alzheimer's disease.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 111 citations in OpenAlex.
- Canonical and noncanonical autophagy in immunity.Immunity · 2026Review
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neuron-derived SPP1 instructs microglia to limit degeneration.Science advances · 2026Article
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer's disease pathology.Nature aging · 2026Article
- L-Leucine Upregulates Lysosomal Biogenesis and Autophagy to Lower Plaques in 5XFAD Mouse Model of Alzheimer's Disease.Journal of neurochemistry · 2026Article
- Nanotechnology-based targeted delivery strategies for the treatment of Alzheimer's disease.Nanoscale advances · 2026Review
- ATG16L1 controls mammalian vacuolar proton ATPase.The Journal of cell biology · 2025Article
- A heterotrimeric protein complex assembles the metazoan V-ATPase upon dissipation of proton gradients.Nature structural & molecular biology · 2025Article
- ATG16L1 WD domain and linker regulates lipid trafficking to maintain plasma membrane integrity to limit influenza virus infection.Autophagy · 2025Article
- Antioxidant, Anti-Inflammatory, and Antiapoptotic Effects ofPlants (Basel, Switzerland) · 2025Review
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- The Hallmarks of Ageing in Microglia.Cellular and molecular neurobiology · 2025Review
- Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.Aging and disease · 2025Review
- An unconventional autophagic pathway that inhibits ATP secretion during apoptotic cell death.Nature communications · 2025Article
- STING-induced noncanonical autophagy regulates endolysosomal homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exploring the multilayered response of TB bacterium Mycobacterial tuberculosis to lysosomal injury.FEMS microbiology reviews · 2025Review
- Natural autophagy modulators in non-communicable diseases: from autophagy mechanisms to therapeutic potential.Acta pharmacologica Sinica · 2025Review
- Canonical and noncanonical autophagy: involvement in Parkinson's disease.Frontiers in cell and developmental biology · 2025Review
- Autophagy and Bacterial infections.Autophagy reports · 2025Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.