Nerve growth factor attenuates oxidant‐induced β‐amyloid neurotoxicity in sporadic Alzheimer’s disease cybrids
Abstract
Although mitochondrial dysfunction has been linked to Alzheimer's disease (AD), it is not fully understood how this dysfunction may induce neuronal death. In this study, we show that transmitochondrial hybrid cells (cybrids) expressing mitochondrial genes from patients with sporadic AD (SAD) have substantial alterations in basal upstream tyrosine kinase signaling and downstream serine-threonine kinase signaling that are mediated by intracellular free radicals. This is associated with reduced tropomyocin receptor kinase (TrkA) and p75 neurotrophin receptor receptor expression that profoundly alters nerve growth factor signaling, increases generation of Aβ and decreases viability. Many of these observed effects in SAD cybrids would be predicted to increase risk of premature neuronal death and reduce resistance to stressors and add further support for the pathogenic role of mtDNA expression in the pathogenesis of SAD.
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Mitochondria directly influence other AD-associated pathologies, particularly APP and Aβ homeostasis.
“Data also argue mitochondria directly influence other AD-associated pathologies, and particularly APP and Aβ homeostasis.”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [172]
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Self-citation
- Authors
- Onyango, I. G., Ahn, J., Tuttle, J. B., Bennett Jr, J. P., & Swerdlow, R. H.
- Affiliations
- University of Kansas Medical Center (US)
- Seoul Medical Center (KR)
- University of Virginia (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2010-09
- Volume
- 114
- Issue
- 6
- Pages
- 1605-1618
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1640499549
- Cited by
- 25
- References
- 66
- Citations by year
- 2023: 3 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 2
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- nerve growth factor, amyloid-beta, sporadic Alzheimer's disease, cybrids, mitochondrial dysfunction, mitochondrial DNA, TrkA, p75 neurotrophin receptor, tyrosine kinase signaling, free radicals, neuronal cell death, neurotoxicity
- MeSH terms
- Acetylcysteine, Aged, Alzheimer Disease, Cell Survival, Cells, Cultured, DNA, Mitochondrial, Female, Glutathione, Humans, Hybrid Cells, Male, Mitochondria, Nerve Growth Factors, Neurons, Peptide Fragments, Phosphorylation, Tyrosine, Signal Transduction, Amyloid beta-Peptides, NF-kappa B, Reactive Oxygen Species, Receptors, Nerve Growth Factor, Receptor, trkA, Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt
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