Telomerase in psychiatry

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Telomerase in psychiatry

  1. 1. Telomerase in PsychiatryIn 1961 Dr. Leonard Hayflick published a now classic paper on cellular aging. According to this articlenormal human cells have a limited capacity for dividing before they die out.Some types of cells, such as those that produce red and white blood cells, can divide millions of times.Others, such as neurons, do not reproduce at all.If a cells Hayflick limit is 50, for example, it will divide50 times and then become senescent, than die. When enough of our cells die, we die.TelomeresA telomere is a repeating sequence of DNA at the end of a chromosome, a sort of cap. Telomeresresemble the aglets on the ends of shoelaces. They keep the ends of the chromosomes from stickingtogether, and from sticking onto other chromosomes. Telomeres are believed to be “cellular clocks” thatset the rate at which the cells age and eventually die.Each time a cell divides, its telomeres shorten. When the telomeres become short enough, cell divisionstops and the cell soon dies. This resembles sharpening a pencil. Each time the pencil is renewed bysharpening, a little bit of it is removed, until after repeated sharpenings, there is no longer enough ofthe pencil remaining to perform its function.TelomeraseA telomerase is an enzyme (ribonucleoprotein polymerase) that was discovered in 1998. Its function ismaintenance and building of new telomeres by addition of the nucleotide repeat TTAGGG. The enzyme consists of a protein component (TERT) with reverse transcriptase activity, and an RNAcomponent, encoded by this gene, that serves as a template for the telomere repeat.
  2. 2. http://www.youtube.com/watch?v=MjfIWzufq_I&noredirect=1Telomerase is present in neuroblastsand early postmitotic embryonic neurons but is absent from adultneurons because they do not reproduce. However,recently it was discovered that the telomeraseprotein TERT is very prevalent in neurons and mitochondria from brain tissue. This suggests thatmitochondrial TERT may protect neurons from oxidative stress known to contribute to age-relateddysfunction and neurodegenerative disease.Telomerase is believed to have a stress-protective function upon the mitochondrion.http://www.crter.org/NRR-E/2009/6k/405-412.pdfThere seems to be a mutual exclusion of TERT and tau proteins in cortical and hippocampal neuronsfrom patients with Alzheimers’ disease (AD).http://brain.oxfordjournals.org/content/134/7/2044.fullApplication in PsychiatryThe role of telomerase in cancer is well documented, but recently, telomere dysfunction in peripheralleukocytes has been described in psychiatric conditions:1. Telomere length is reduced in peripheral blood lymphocytes from individuals with schizophreniaprobably due to decreased telomerase activity.Further studies are needed since this is avalid candidate for a biological marker in this condition (Kao etal., 2008; Porton et al., 2008).2. Accelerated telomere shortening and decreased telomerase activity has been reported in chronicallystressed individuals (Epel et al., 2004), mood disorders (Simon et al., 2006).http://www.jneurosci.org/content/31/34/12258.full.pdf3. Mice deficient in mTERT exhibited significantly altered anxiety-like behaviors (Lee et al., 2010).http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.00178374. Exposure to violence in childhood short telomereshttp://www.moffittcaspi.com/WhatsNew/Shalev_2012_MPepub.pdfADONIS SFERA, MD

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