The DOI matches its Crossref record; 61 of the 62 references it cites were found in a registry or an index.
Microglial Beclin 1 Regulates Retromer Trafficking and Phagocytosis and Is Impaired in Alzheimer’s Disease
Open accessAbstract
Phagocytosis controls CNS homeostasis by facilitating the removal of unwanted cellular debris. Accordingly, impairments in different receptors or proteins involved in phagocytosis result in enhanced inflammation and neurodegeneration. While various studies have identified extrinsic factors that modulate phagocytosis in health and disease, key intracellular regulators are less understood. Here we show that the autophagy protein beclin 1 is required for efficient phagocytosis in vitro and in mouse brains. Furthermore, we show that beclin 1-mediated impairments in phagocytosis are associated with dysfunctional recruitment of retromer to phagosomal membranes, reduced retromer levels, and impaired recycling of phagocytic receptors CD36 and Trem2. Interestingly, microglia isolated from human Alzheimer's disease (AD) brains show significantly reduced beclin 1 and retromer protein levels. These findings position beclin 1 as a link between autophagy, retromer trafficking, and receptor-mediated phagocytosis and provide insight into mechanisms by which phagocytosis is regulated and how it may become impaired in AD.
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“Although the beads are not physiological substrates of phagocytes, they serve as experimental substrates to probe phagocytic response under in vitro experimental conditions [37].”
From Multifaceted response of microglia in the cuprizone model of demyelination (2026) · cites this paper as [37]
In the citing paper
“microglial phagocytosis of Aβ deposits in Alzheimer disease models [430,431] requires the autophagy-related factors BECN1, ATG7 and LC3 [432,433].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [433]
In the citing paper
“autophagy may also enhance microglial clearance of Aβ”
From TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease (2017) · cites this paper as Lucin et al., 2013
In the citing paper
“and that this protein is decreased in microglia from AD brains [153].”
From Microglial dysfunction in brain aging and Alzheimer's disease (2014) · cites this paper as [153]
In the citing paper
“a study from our laboratory recently demonstrated that genetic-reduction of beclin 1, a protein classically associated with the autophagy degradation pathway, disrupted phagocytosis and retromer-mediated recycling of the phagocytic receptors CD36 and TREM2 in microglia”
From Microglial dysfunction in brain aging and Alzheimer's disease (2014) · cites this paper as [153]
In the citing paper
“The expression of several autophagy proteins, in particular Beclin1, ATG5, and ATG7, decline with age, and is exacerbated in AD (Lipinski et al., 2010; Lucin et al., 2013; Pickford et al., 2008; Rubinsztein et al., 2011).”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Lucin et al., 2013
In the citing paper
“The Legionella-derived protease, RavZ, which irreversibly cleaves lipidated LC3 (Choy et al., 2012; Kwon et al., 2017) also prevented this receptor recycling, again, as defined by this method (Lucin et al., 2013; Yin et al., 2016).”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Lucin et al., 2013
In the citing paper
“A previous study had shown that this recycling of CD36 and TREM2 is dependent on Beclin1 and VPS34 (Lucin et al., 2013), which we confirmed in primary BMDM (Fig. 3).”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Lucin et al., 2013
In the citing paper
“According to the receptor-recycling method we employed and established by others (Lucin et al., 2013; Yin et al., 2016), we found that LANDO is required for the recycling of putative Aβ receptors (CD36, TREM2, and TLR4) from internalized endosomes to the plasma membrane.”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Lucin et al., 2013
In the citing paper
“This method is well-established and used as previously reported (Lucin et al., 2013).”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Lucin et al., 2013
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Citations
Cites
2 retracted
Martinez, J., Almendinger, J., Oberst, A., Ness, R., Dillon, C. P., Fitzgerald, P., Hengartner, M. O., & Green, D. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113421108 · Cited by 655 · cited 1×
“Although inhibiting beclin 1 is likely to affect various cellular processes that could influence substrate clearance, including autophagy and potentially phagosomal maturation (which has been described for phagosomes containing apoptotic cells, entotic cells, and bacteria (Berger et al., 2010; Florey et al., 2011; Ma…”
RetractedCrews, L. A., Spencer, B. J., Desplats, P., Patrick, C., Paulino, A., Rockenstein, E. M., Hansen, L. A., Adame, A., Galasko, D. R., & Masliah, E. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009313 · Cited by 379
Self-citationRetractedResting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Autophagy in immunity and inflammation
Levine, B., Mizushima, N., & Virgin, H. W. (2011) · Nature · doi:10.1038/nature09782 · Cited by 3,289
TREM2 Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020
NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., et al. (2013) · Nature · doi:10.1038/nature11729 · Cited by 2,898
The role of autophagy during the early neonatal starvation period
Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., & Mizushima, N. (2004) · Nature · doi:10.1038/nature03029 · Cited by 2,865
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
Impairment of starvation-induced and constitutive autophagy in Atg7 -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331
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Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
Self-citationImmune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134
TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease
Ulland, T. K., Song, W. M., Huang, S. C.-C., Ulrich, J. D., Sergushichev, A., Beatty, W. L., Loboda, A. A., Zhou, Y., Cairns, N. J., Kambal, A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.023 · Cited by 1,263
Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease
Prinz, M., & Priller, J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3722 · Cited by 1,329
The clearance of dead cells by efferocytosis
Boada-Romero, E., Martinez, J., Heckmann, B. L., & Green, D. R. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0232-1 · Cited by 924
Metadata
- Authors
- Lucin, K. M., O’Brien, C. E., Bieri, G., Czirr, E., Mosher, K. I., Abbey, R. J., Mastroeni, D. F., Rogers, J., Spencer, B., Masliah, E., & Wyss-Coray, T.
- Affiliations
- VA Palo Alto Health Care System (US)
- Banner Sun Health Research Institute (US)
- SRI International (US)
- University of California San Diego (US)
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 79
- Issue
- 5
- Pages
- 873-886
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3779465
- OpenAlex
- W2081014274
- Cited by
- 374
- References
- 62
- Citations by year
- 2026: 11 · 2025: 23 · 2024: 27 · 2023: 34 · 2022: 38 · 2021: 37 · 2020: 30 · 2019: 37 · 2018: 28 · 2017: 24 · 2016: 23 · 2015: 33 · 2014: 27 · 2013: 2
- FWCI
- 15.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- U.S. Department of Veterans Affairs (I01 BX001319)
- University of California, Irvine
- National Institute on Aging (P30-AG-19610, F31AG040877, R01 AG10435, R01AG18440, R37AG018440, R01AG018440, P50AG005131, R01AG020603, R01AG030144, R01AG045034, P30AG019610, R01AG043384)
- National Institute of Mental Health (T32MH020016)
- National Institute of Neurological Disorders and Stroke (P30NS069375, F31NS078865, U24NS072026)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- Beclin-1, retromer complex, phagocytosis, microglia, Alzheimer's disease, autophagy, CD36, TREM2, receptor recycling, neuroinflammation, neurodegeneration
- MeSH terms
- Beclin-1, Alzheimer Disease, Animals, Autophagy, Brain, Cell Line, Humans, Membrane Glycoproteins, Membrane Proteins, Phagocytosis, Receptors, Immunologic, Amyloid beta-Peptides, Microglia, CD36 Antigens, Vesicular Transport Proteins, Apoptosis Regulatory Proteins, Mice
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