Abstract
Amyloid-β (Aβ) peptides, widely presumed to cause Alzheimer's disease, increased mouse neuronal expression of collagen VI through a mechanism involving transforming growth factor signaling. Reduction of collagen VI augmented Aβ neurotoxicity, whereas treatment of neurons with soluble collagen VI blocked the association of Aβ oligomers with neurons, enhanced Aβ aggregation and prevented neurotoxicity. These results identify collagen VI as an important component of the neuronal injury response and demonstrate its neuroprotective potential.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cheng, I.H. et al. J. Biol. Chem. 282, 23818–23828 (2007).
Palop, J.J. et al. J. Neurosci. 25, 9686–9693 (2005).
Palop, J.J. et al. Neuron 55, 697–711 (2007).
Mucke, L. et al. J. Neurosci. 20, 4050–4058 (2000).
Lorenzo, A. et al. Nat. Neurosci. 3, 460–464 (2000).
Beher, D., Hesse, L., Masters, C.L. & Multhaup, G. J. Biol. Chem. 271, 1613–1620 (1996).
Wyss-Coray, T. et al. Nat. Med. 9, 453–457 (2003).
Verrecchia, F., Chu, M.L. & Mauviel, A. J. Biol. Chem. 276, 17058–17062 (2001).
Massagué, J., Seoane, J. & Wotton, D. Genes Dev. 19, 2783–2810 (2005).
Tesseur, I. et al. J. Clin. Invest. 116, 3060–3069 (2006).
Irwin, W.A. et al. Nat. Genet. 35, 367–371 (2003).
Bonaldo, P. et al. Hum. Mol. Genet. 7, 2135–2140 (1998).
Chernoff, E.A.G. & Chernoff, D.A. J. Vac. Sci. Technol. 10, 596–599 (1992).
Lacor, P.N. et al. J. Neurosci. 24, 10191–10200 (2004).
Burdick, D., Kosmoski, J., Knauer, M.F. & Glabe, C.G. Brain Res. 746, 275–284 (1997).
Acknowledgements
We thank H. Solanoy, X. Wang, G.-Q. Yu and Y. Zhou for excellent technical support, S. Maeda for helpful discussions on AFM, P. Scherer for α1(VI)-deficient mice, R. Jaenisch for CamK-Cre93 transgenic mice, H. Moses for TβRIIfl/fl knockin mice, C. Weissmann for APP-deficient mice, M.-L. Chu for the Col6a1 cDNA, the New York Brain Bank at Columbia University Medical Center for human tissues, G. Howard and S. Ordway for editorial review, J. Carroll, T. Roberts and C. Goodfellow for preparation of graphics, and D. McPherson for administrative assistance. Confocal images were acquired at the Nikon Imaging Center at University of California, San Francisco. This work was supported by grants from the US National Institutes of Health, a medical student fellowship from the Howard Hughes Medical Institute, a Larry L. Hillblom Fellowship and a facilities grant from the National Center for Research Resources.
Author information
Authors and Affiliations
Contributions
J.S.C. and D.B.D. conducted the experiments and wrote the manuscript. J.L. performed atomic force microscopy analysis. I.H.C. prepared oligomeric Aβ. I.T., T.W.-C. and P.B. provided animal models and helpful discussions. D.H.K. and G.-Q.Y. provided technical assistance. L.M. supervised the project.
Note: Supplementary information is available on the Nature Neuroscience website.
Corresponding author
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–3 and Supplementary Methods (PDF 5183 kb)
Rights and permissions
About this article
Cite this article
Cheng, J., Dubal, D., Kim, D. et al. Collagen VI protects neurons against Aβ toxicity. Nat Neurosci 12, 119–121 (2009). https://doi.org/10.1038/nn.2240
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn.2240
This article is cited by
-
Collagen in the central nervous system: contributions to neurodegeneration and promise as a therapeutic target
Molecular Neurodegeneration (2024)
-
PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons
Nature Neuroscience (2024)
-
Contextual fear memory impairment in Angelman syndrome model mice is associated with altered transcriptional responses
Scientific Reports (2023)
-
Mapping the dynamics of insulin-responsive pathways in the blood–brain barrier endothelium using time-series transcriptomics data
npj Systems Biology and Applications (2022)
-
Matrisome changes in Parkinson’s disease
Analytical and Bioanalytical Chemistry (2022)