NO synthase 2 ( NOS2 ) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease
Abstract
Alzheimer's disease is characterized by two primary pathological features: amyloid plaques and neurofibrillary tangles. The interconnection between amyloid and tau aggregates is of intense interest, but mouse models have yet to reveal a direct interrelationship. We now show that NO may be a key factor that connects amyloid and tau pathologies. Genetic removal of NO synthase 2 in mice expressing mutated amyloid precursor protein results in pathological hyperphosphorylation of mouse tau, its redistribution to the somatodendritic compartment in cortical and hippocampal neurons, and aggregate formation. Lack of NO synthase 2 in the amyloid precursor protein Swedish mutant mouse increased insoluble β-amyloid peptide levels, neuronal degeneration, caspase-3 activation, and tau cleavage, suggesting that NO acts at a junction point between β-amyloid peptides, caspase activation, and tau aggregation.
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iNOS deficiency also caused significant tau pathology in the APPSwDI model.
“iNOS deficiency also caused significant tau pathology.459”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [459]
In an APPSwDI transgenic mouse model, iNOS deficiency results in significant neuron loss in disease-relevant regions and further cognitive decline despite unaltered levels of Aβ.
“In a APPSwDI transgenic mouse model, iNOS deficiency results in significant neuron loss in disease-relevant regions and further cognitive decline in behavioral tests despite unaltered levels of Aβ.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [459]
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- Authors
- Colton, C. A., Vitek, M. P., Wink, D. A., Xu, Q., Cantillana, V., Previti, M. L., Van Nostrand, W. E., Weinberg, J. B., & Dawson, H.
- Affiliations
- Duke University (US)
- *Division of Neurology, and
- National Institutes of Health (US)
- Stony Brook University (US)
- Department of Medicine, Stony Brook University, Stony Brook, NY 11794
- Duke Medical Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-08-22
- Volume
- 103
- Issue
- 34
- Pages
- 12867-12872
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1964053234
- Cited by
- 128
- References
- 5
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 13 · 2013: 6 · 2012: 5
- FWCI
- 5.76
- Type
- journal article
- Language
- en
- Update notices
- correction (2006-10-10)
- Open access
- closed
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG19780, AG19740, R01AG019740, R01AG019780)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, nitric oxide synthase 2, amyloid plaques, amyloid-beta, tau hyperphosphorylation, tau aggregation, caspase-3 activation, neurodegeneration, neurofibrillary tangles
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Phosphorylation, Amyloid beta-Peptides, tau Proteins, Gene Deletion, Mice, Knockout, Caspases, Mice, Nitric Oxide Synthase Type II, Caspase 3
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