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Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation.
Neuron. 2011 Sep 08; 71(5):833-44.N

Abstract

Part of the inflammatory response in Alzheimer's disease (AD) is the upregulation of the inducible nitric oxide synthase (NOS2) resulting in increased NO production. NO contributes to cell signaling by inducing posttranslational protein modifications. Under pathological conditions there is a shift from the signal transducing actions to the formation of protein tyrosine nitration by secondary products like peroxynitrite and nitrogen dioxide. We identified amyloid β (Aβ) as an NO target, which is nitrated at tyrosine 10 (3NTyr(10)-Aβ). Nitration of Aβ accelerated its aggregation and was detected in the core of Aβ plaques of APP/PS1 mice and AD brains. NOS2 deficiency or oral treatment with the NOS2 inhibitor L-NIL strongly decreased 3NTyr(10)-Aβ, overall Aβ deposition and cognitive dysfunction in APP/PS1 mice. Further, injection of 3NTyr(10)-Aβ into the brain of young APP/PS1 mice induced β-amyloidosis. This suggests a disease modifying role for NOS2 in AD and therefore represents a potential therapeutic target.

Authors+Show Affiliations

Clinical Neuroscience Unit, Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21903077

Citation

Kummer, Markus P., et al. "Nitration of Tyrosine 10 Critically Enhances Amyloid Β Aggregation and Plaque Formation." Neuron, vol. 71, no. 5, 2011, pp. 833-44.
Kummer MP, Hermes M, Delekarte A, et al. Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation. Neuron. 2011;71(5):833-44.
Kummer, M. P., Hermes, M., Delekarte, A., Hammerschmidt, T., Kumar, S., Terwel, D., Walter, J., Pape, H. C., König, S., Roeber, S., Jessen, F., Klockgether, T., Korte, M., & Heneka, M. T. (2011). Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation. Neuron, 71(5), 833-44. https://doi.org/10.1016/j.neuron.2011.07.001
Kummer MP, et al. Nitration of Tyrosine 10 Critically Enhances Amyloid Β Aggregation and Plaque Formation. Neuron. 2011 Sep 8;71(5):833-44. PubMed PMID: 21903077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation. AU - Kummer,Markus P, AU - Hermes,Michael, AU - Delekarte,Andrea, AU - Hammerschmidt,Thea, AU - Kumar,Sathish, AU - Terwel,Dick, AU - Walter,Jochen, AU - Pape,Hans-Christian, AU - König,Simone, AU - Roeber,Sigrun, AU - Jessen,Frank, AU - Klockgether,Thomas, AU - Korte,Martin, AU - Heneka,Michael T, PY - 2011/07/01/accepted PY - 2011/9/10/entrez PY - 2011/9/10/pubmed PY - 2011/10/29/medline SP - 833 EP - 44 JF - Neuron JO - Neuron VL - 71 IS - 5 N2 - Part of the inflammatory response in Alzheimer's disease (AD) is the upregulation of the inducible nitric oxide synthase (NOS2) resulting in increased NO production. NO contributes to cell signaling by inducing posttranslational protein modifications. Under pathological conditions there is a shift from the signal transducing actions to the formation of protein tyrosine nitration by secondary products like peroxynitrite and nitrogen dioxide. We identified amyloid β (Aβ) as an NO target, which is nitrated at tyrosine 10 (3NTyr(10)-Aβ). Nitration of Aβ accelerated its aggregation and was detected in the core of Aβ plaques of APP/PS1 mice and AD brains. NOS2 deficiency or oral treatment with the NOS2 inhibitor L-NIL strongly decreased 3NTyr(10)-Aβ, overall Aβ deposition and cognitive dysfunction in APP/PS1 mice. Further, injection of 3NTyr(10)-Aβ into the brain of young APP/PS1 mice induced β-amyloidosis. This suggests a disease modifying role for NOS2 in AD and therefore represents a potential therapeutic target. SN - 1097-4199 UR - https://www.unboundmedicine.com/medline/citation/21903077/Nitration_of_tyrosine_10_critically_enhances_amyloid_β_aggregation_and_plaque_formation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0896-6273(11)00595-2 DB - PRIME DP - Unbound Medicine ER -