The Catalytic Subunit of Telomerase Protects Neurons Against Amyloid β‐Peptide‐Induced Apoptosis
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Abstract : The catalytic subunit of telomerase (TERT) is a specialized reverse transcriptase that has been associated with cell immortalization and cancer. It was reported recently that TERT is expressed in neurons throughout the brain in embryonic and early postnatal development, but is absent from neurons in the adult brain. We now report that suppression of TERT levels and function in embryonic mouse hippocampal neurons in culture using antisense technology and the telomerase inhibitor 3' ‐azido‐2' 3' ‐dideoxythymidine significantly increases their vulnerability to cell death induced by amyloid β‐peptide, a neurotoxic protein believed to promote neuronal degeneration in Alzheimer's disease. Neurons in which TERT levels were reduced exhibited increased levels of oxidative stress and mitochondrial dysfunction following exposure to amyloid β‐peptide. Overexpression of TERT in pheochromocytoma cells resulted in decreased vulnerability to amyloid β‐peptide‐induced apoptosis. Our findings demonstrate a neuroprotective function of TERT in an experimental model relevant to Alzheimer's disease, and suggest the possibility that restoration of TERT expression in neurons in the adult brain may protect against age‐related neurodegeneration.
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Telomerase appears to protect against amyloid-β-induced cell death in embryonic mouse hippocampal neurons in vitro.
“and against amyloid-β-induced cell death in embryonic mouse hippocampal neurons in vitro166”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [166]
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- Authors
- Zhu, H., Fu, W., & Mattson, M. P.
- Affiliations
- University of Kentucky (US)
- National Institutes of Health (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2000-07
- Volume
- 75
- Issue
- 1
- Pages
- 117-124
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2071245320
- Cited by
- 175
- References
- 64
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 10 · 2012: 3
- FWCI
- 7.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- telomerase reverse transcriptase, amyloid-beta, neuronal apoptosis, neuroprotection, Alzheimer's disease, oxidative stress, mitochondrial dysfunction, hippocampal neurons, telomerase inhibitors, zidovudine, age-related neurodegeneration
- MeSH terms
- Alzheimer Disease, Animals, Cells, Cultured, DNA-Binding Proteins, Embryo, Mammalian, Enzyme Inhibitors, Hippocampus, Immunohistochemistry, Mitochondria, Neurons, RNA, Gene Expression, Amyloid beta-Peptides, Oligonucleotides, Antisense, PC12 Cells, Apoptosis, Oxidative Stress, Telomerase, Catalytic Domain, Mice, Rats
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