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 maint aining their length and preventing cell cycle arrest and cell death (cellul ar senescence). During development of the nervous system, telomerase activi ty levels are high in neural progenitor cells, but then they decrease as ce lls differentiate or die. The catalytic subunit of telomerase (TERT) remain s at relatively high levels during the process of neuronal differentiation and then decreases sharply during the period when synapses form and program med cell death occurs. TERT promotes survival of developing brain neurons. Suppression of telomerase activity and TERT expression promotes apoptosis o f neurons, whereas overexpression of TERT prevents apoptosis by suppressing cell death at a premitochondrial step in the death cascade TERT may suppre ss DNA damage and/or apoptotic signals activated by damaged DNA. Recent stu dies of the transcriptional regulation of the TERT gene suggest that this e nzyme may mediate the cell survival-promoting actions of diverse signals in cluding estrogen, cytokines and neurotrophic factors. The elucidation of th e functions of telomerase activity and TERT in neuronal differentiation and survival may lead to novel approaches for preventing neuronal death and pr omoting recovery of function in various neurodegenerative conditions. (C) 2 001 Published by Elsevier Science Ireland Ltd.