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Telomerase protects developing neurons against DNA damage-induced cell death
C Lu1, W Fu, M P Mattson
1Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Brain Research. Developmental Brain Research
|November 24, 2001
Summary
Telomerase (TERT) protects neurons from DNA damage-induced death. This finding suggests TERT may play a role in preventing neuronal death during brain development and in neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Telomerase, a key enzyme in DNA replication, adds repeats to chromosome ends, maintaining telomere length and preventing cellular senescence.
- The catalytic subunit of telomerase (TERT) is expressed in developing rodent brain neuronal progenitor cells and early postmitotic neurons.
Purpose of the Study:
- To investigate the role of telomerase (TERT) in protecting neurons against DNA damage-induced cell death.
- To determine if TERT expression influences neuronal vulnerability to DNA-damaging agents.
Main Methods:
- Overexpression of TERT in PC12 cells and embryonic hippocampal neurons.
- Utilizing antisense technology to decrease TERT levels in hippocampal neurons.
- Assessing cell viability following exposure to DNA-damaging agents like camptothecin and etoposide.
Main Results:
- Overexpression of TERT enhanced the resistance of PC12 cells to topoisomerase inhibitors.
- Reduced TERT levels in hippocampal neurons increased their vulnerability to DNA-damaging agents.
- TERT demonstrated a protective effect against DNA damage-induced cell death in cultured neurons.
Conclusions:
- TERT plays a significant role in protecting neurons from DNA damage-induced death.
- TERT may be a potential therapeutic target for neurodegenerative disorders characterized by DNA damage.
- These findings highlight a novel function of TERT beyond its established role in telomere maintenance.