The DOI matches its Crossref record; 109 of the 109 references it cites were found in a registry or an index.
Amyloid beta oligomers induce impairment of neuronal insulin receptors
Abstract
Recent studies have indicated an association between Alzheimer's disease (AD) and central nervous system (CNS) insulin resistance. However, the cellular mechanisms underlying the link between these two pathologies have not been elucidated. Here we show that signal transduction by neuronal insulin receptors (IR) is strikingly sensitive to disruption by soluble Abeta oligomers (also known as ADDLs). ADDLs are known to accumulate in AD brain and have recently been implicated as primary candidates for initiating deterioration of synapse function, composition, and structure. Using mature cultures of hippocampal neurons, a preferred model for studies of synaptic cell biology, we found that ADDLs caused a rapid and substantial loss of neuronal surface IRs specifically on dendrites bound by ADDLs. Removal of dendritic IRs was associated with increased receptor immunoreactivity in the cell body, indicating redistribution of the receptors. The neuronal response to insulin, measured by evoked IR tyrosine autophosphorylation, was greatly inhibited by ADDLs. Inhibition also was seen with added glutamate or potassium-induced depolarization. The effects on IR function were completely blocked by NMDA receptor antagonists, tetrodotoxin, and calcium chelator BAPTA-AM. Downstream from the IR, ADDLs induced a phosphorylation of Akt at serine473, a modification associated with neurodegenerative and insulin resistance diseases. These results identify novel factors that affect neuronal IR signaling and suggest that insulin resistance in AD brain is a response to ADDLs, which disrupt insulin signaling and may cause a brain-specific form of diabetes as part of an overall pathogenic impact on CNS synapses.
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“Aβ oligomers induce a striking redistribution of IRs, causing their internalization from dendritic membranes and accumulation in the cell body. This renders neurons insulin resistant (De Felice et al., 2009; De Felice et al., 2008; Zhao et al., 2008).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Zhao et al., 2008
Citations
Cites
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291
Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506
Self-citationPathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052
Critical nodes in signalling pathways: insights into insulin action
Taniguchi, C. M., Emanuelli, B., & Kahn, C. R. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1837 · Cited by 2,760
AMPA Receptor Trafficking and Synaptic Plasticity
Malinow, R., & Malenka, R. C. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142758 · Cited by 2,588
Natural oligomers of the amyloid-β protein specifically disrupt cognitive function
Cleary, J. P., Walsh, D. M., Hofmeister, J. J., Shankar, G. M., Kuskowski, M. A., Selkoe, D. J., & Ashe, K. H. (2004) · Nature Neuroscience · doi:10.1038/nn1372 · Cited by 1,722
Steen, E., Terry, B. M., J. Rivera, E., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2005-7107 · Cited by 1,703
Regulation of NMDA receptor trafficking by amyloid-β
Snyder, E. M., Nong, Y., Almeida, C. G., Paul, S., Moran, T., Choi, E. Y., Nairn, A. C., Salter, M. W., Lombroso, P. J., Gouras, G. K., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561 · cited 3×
“The redistribution of IRs is consistent with reports in which other proteins important for synaptic plasticity, including NMDA receptor subunits and EphB2 receptor tyrosine kinase, also show surface loss caused by soluble forms of A (56, 69).”
Deciphering the Molecular Basis of Memory Failure in Alzheimer's Disease
Walsh, D. M., & Selkoe, D. J. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.010 · Cited by 1,207
Research works printed but not linked: 8
- Abramoff M. D., 2004, Image processing with Image, J. Biophotonics Int., 11, 36
- 10.1161/01.RES.0000152968.71868.c3 · DOI
- Stevens G. R.(1998)Signaling proteins in Alzheimer's Disease: The possible roles of focal adhesion kinase paxillin and protein kinase C. Ph.D. thesis pp.101–112 Northwestern University
- 10.1007/s001250050761 · DOI
- Stevens G. R.(1998)Signaling proteins in Alzheimer's Disease: the possible roles of focal adhesion kinase paxillin and protein kinase C. Ph.D. thesis pp101–112 Northwestern University
- 10.1161/01.RES.0000152968.71868.c3 · DOI
- 10.1007/BF02980074 · DOI
- 10.1038/41792 · DOI
Cited by
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Talbot, K., Wang, H.-Y., Kazi, H., Han, L.-Y., Bakshi, K. P., Stucky, A., Fuino, R. L., Kawaguchi, K. R., Samoyedny, A. J., Wilson, R. S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59903 · Cited by 1,871
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870
Self-citationBomfim, T. R., Forny‐Germano, L., Sathler, L. B., Brito‐Moreira, J., Houzel, J., Decker, H., Silverman, M. A., Kazi, H., Melo, H. M., McClean, P. L., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci57256 · Cited by 849
Moloney, A. M., Griffin, R. J., Timmons, S., O’Connor, R., Ravid, R., & O’Neill, C. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.04.002 · Cited by 764
Chen, Z., & Zhong, C. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.06.004 · Cited by 698
Metadata
- Authors
- Zhao, W., De Felice, F. G., Fernandez, S., Chen, H., Lambert, M. P., Quon, M. J., Krafft, G. A., & Klein, W. L.
- Affiliations
- Department of Neurobiology and Physiology Northwestern University Evanston Illinois USA
- Northwestern University (US)
- National Institutes of Health (US)
- Blanchette Rockefeller Neurosciences Institute (US)
- Acumen Pharmaceuticals (United States) (US)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2007-08-24
- Volume
- 22
- Issue
- 1
- Pages
- 246-260
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2144486959
- Semantic Scholar
- 0a3dc4e52b02b85d3d180f43a62aee9078ca629b
- Cited by
- 587
- References
- 109
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 21 · 2023: 22 · 2022: 37 · 2021: 34 · 2020: 28 · 2019: 29 · 2018: 38 · 2017: 42 · 2016: 51 · 2015: 46 · 2014: 35 · 2013: 30 · 2012: 39
- FWCI
- 14.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (RO1‐AG18877)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta oligomers, Alzheimer's disease, insulin resistance, insulin signaling, tyrosine autophosphorylation, NMDA receptor, Akt phosphorylation, hippocampal neurons, synaptic dysfunction
- MeSH terms
- Animals, Biopolymers, Cells, Cultured, Dendrites, Humans, Insulin, Neurons, Phosphorylation, Protein-Tyrosine Kinases, Receptor, Insulin, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Amyloid beta-Peptides, Rats, Sprague-Dawley, Rats
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