Emerging roles for telomerase in regulating cell differentiation and survival: a neuroscientist's perspective

Telomerase is a reverse transcriptase that adds repeats of a DNA sequence (TTAGGG) to the ends of chromosomes (telomeres) in mitotic cells, thus maintaining their length and preventing cell cycle arrest and cell death (cellular senescence). During development of the nervous system, telomerase activity levels are high in neural progenitor cells, but then they decrease as cells differentiate or die. The catalytic subunit of telomerase (TERT) remains at relatively high levels during the process of neuronal differentiation and then decreases sharply during the period when synapses form and programmed cell death occurs. TERT promotes survival of developing brain neurons. Suppression of telomerase activity and TERT expression promotes apoptosis of neurons, whereas overexpression of TERT prevents apoptosis by suppressing cell death at a premitochondrial step in the death cascade TERT may suppress DNA damage and/or apoptotic signals activated by damaged DNA. Recent studies of the transcriptional regulation of the TERT gene suggest that this enzyme may mediate the cell survival-promoting actions of diverse signals including estrogen, cytokines and neurotrophic factors. The elucidation of the functions of telomerase activity and TERT in neuronal differentiation and survival may lead to novel approaches for preventing neuronal death and promoting recovery of function in various neurodegenerative conditions. (C) 2001 Published by Elsevier Science Ireland Ltd.