The long and short of it: telomeres and the brain.

摘要

The 2006 Albert Lasker Award for Basic Medical Research was awarded to Elizabeth Blackburn at University of California San Francisco, Carol Greider at Johns Hopkins University, and Jack Szostak at Harvard Medical School "for the prediction and discovery of telomerase, a remarkable RNA-containing enzyme that synthesizes the ends of chromosomes, protecting them and maintaining the integrity of the genome".Telomerase is a reverse transcriptase complex that provides an essential maintenance function for chromosomal ends, ortelomeres, during replication.The telomerase complex consists of the enzyme and an RNA template, and interacts with the nuclear machinery for maintenance of genomic integrity, chromatin assembly, and DNA repair. Human telomeres consist of many copies of a uniform double-stranded sequence of DNA, ending with an overhanging single-stranded sequence. Generally, telomeres shorten with cell division, with the exception of post-mitotic cells, such as neurons, which do not divide and thus telomere length is static. The absence of telomerase function engineered in cultured cells and in murine models leads to progressive telomere shortening and cell senescence, whereas overexpression of telomerase immortalises cells in culture and can transform them into a premalignant state. Mature primary cells do not express telomerase in culture and therefore have limited life spans. By contrast, fetal progenitor stem cells of different lineages, including neural stem cells, express telomerase and maintain their telomeric length with proliferation.