The catalytic subunit of telomerase protects neurons against amyloid β- peptide-induced apoptosis

Haiyan Zhu, Weiming Fu, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

The catalytic subunit of telomerase (TERT) is a specialize 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.

Original languageEnglish (US)
Pages (from-to)117-124
Number of pages8
JournalJournal of Neurochemistry
Volume75
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • 3'-Azido-2',3'- dideoxythymidine
  • Alzheimer's disease
  • Caspase
  • Mitochondrial transmembrane potential
  • Reverse transcriptase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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