Literature DB >> 33946850

Telomerase in Brain: The New Kid on the Block and Its Role in Neurodegenerative Diseases.

Gabriele Saretzki1, Tengfei Wan1.   

Abstract

Telomerase is an enzyme that in its canonical function extends and maintains telomeres, the ends of chromosomes. This reverse transcriptase function is mainly important for dividing cells that shorten their telomeres continuously. However, there are a number of telomere-independent functions known for the telomerase protein TERT (Telomerase Reverse Transcriptase). This includes the shuttling of the TERT protein from the nucleus to mitochondria where it decreases oxidative stress, apoptosis sensitivity and DNA damage. Recently, evidence has accumulated on a protective role of TERT in brain and postmitotic neurons. This function might be able to ameliorate the effects of toxic proteins such as amyloid-β, pathological tau and α-synuclein involved in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, the protective mechanisms of TERT are not clear yet. Recently, an activation of autophagy as an important protein degradation process for toxic neuronal proteins by TERT has been described. This review summarises the current knowledge about the non-canonical role of the telomerase protein TERT in brain and shows its potential benefit for the amelioration of brain ageing and neurodegenerative diseases such as AD and PD. This might form the basis for the development of novel strategies and therapies against those diseases.

Entities:  

Keywords:  TERT protein; autophagy; brain; neurodegenerative disease; neuron; telomerase

Year:  2021        PMID: 33946850     DOI: 10.3390/biomedicines9050490

Source DB:  PubMed          Journal:  Biomedicines        ISSN: 2227-9059


  82 in total

1.  Subnuclear shuttling of human telomerase induced by transformation and DNA damage.

Authors:  Judy M Y Wong; Leonard Kusdra; Kathleen Collins
Journal:  Nat Cell Biol       Date:  2002-09       Impact factor: 28.824

2.  Nuclear import of hTERT requires a bipartite nuclear localization signal and Akt-mediated phosphorylation.

Authors:  Jeeyun Chung; Prabhat Khadka; In Kwon Chung
Journal:  J Cell Sci       Date:  2012-02-24       Impact factor: 5.285

3.  Excitotoxic and Radiation Stress Increase TERT Levels in the Mitochondria and Cytosol of Cerebellar Purkinje Neurons.

Authors:  Erez Eitan; Carmel Braverman; Ailone Tichon; Daniel Gitler; Emmette R Hutchison; Mark P Mattson; Esther Priel
Journal:  Cerebellum       Date:  2016-08       Impact factor: 3.847

4.  The telomerase reverse transcriptase regulates chromatin state and DNA damage responses.

Authors:  Kenkichi Masutomi; Richard Possemato; Judy M Y Wong; Jennifer L Currier; Zuzana Tothova; Judith B Manola; Shridar Ganesan; Peter M Lansdorp; Kathleen Collins; William C Hahn
Journal:  Proc Natl Acad Sci U S A       Date:  2005-05-31       Impact factor: 11.205

5.  IL-2 increases human telomerase reverse transcriptase activity transcriptionally and posttranslationally through phosphatidylinositol 3'-kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells.

Authors:  Kiyotaka Kawauchi; Kimiko Ihjima; Osamu Yamada
Journal:  J Immunol       Date:  2005-05-01       Impact factor: 5.422

6.  Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via Src kinase family-dependent phosphorylation of tyrosine 707.

Authors:  Judith Haendeler; Jörg Hoffmann; Ralf P Brandes; Andreas M Zeiher; Stefanie Dimmeler
Journal:  Mol Cell Biol       Date:  2003-07       Impact factor: 4.272

7.  Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria.

Authors:  Satomi Miwa; Rafal Czapiewski; Tengfei Wan; Amy Bell; Kirsten N Hill; Thomas von Zglinicki; Gabriele Saretzki
Journal:  Aging (Albany NY)       Date:  2016-10-22       Impact factor: 5.682

8.  Expression of functional alternative telomerase RNA component gene in mouse brain and in motor neurons cells protects from oxidative stress.

Authors:  Erez Eitan; Admoni Tamar; Grin Yossi; Refael Peleg; Alex Braiman; Esther Priel
Journal:  Oncotarget       Date:  2016-11-29

Review 9.  Composition and Function of Telomerase-A Polymerase Associated with the Origin of Eukaryotes.

Authors:  Petra Procházková Schrumpfová; Jiří Fajkus
Journal:  Biomolecules       Date:  2020-10-08

10.  Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response.

Authors:  Diana Jurk; Chunfang Wang; Satomi Miwa; Mandy Maddick; Viktor Korolchuk; Avgi Tsolou; Efstathios S Gonos; Christopher Thrasivoulou; M Jill Saffrey; Kerry Cameron; Thomas von Zglinicki
Journal:  Aging Cell       Date:  2012-09-12       Impact factor: 9.304

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  5 in total

Review 1.  Telomeres and Mitochondrial Metabolism: Implications for Cellular Senescence and Age-related Diseases.

Authors:  Xingyu Gao; Xiao Yu; Chang Zhang; Yiming Wang; Yanan Sun; Hui Sun; Haiying Zhang; Yingai Shi; Xu He
Journal:  Stem Cell Rev Rep       Date:  2022-04-23       Impact factor: 6.692

2.  Reversal of brain aging by targeting telomerase: A nutraceutical approach.

Authors:  Dimitris Tsoukalas; Ana Maria Buga; Anca Oana Docea; Evangelia Sarandi; Radu Mitrut; Elisavet Renieri; Demetrios A Spandidos; Ion Rogoveanu; Liliana Cercelaru; Mihaela Niculescu; Aristidis Tsatsakis; Daniela Calina
Journal:  Int J Mol Med       Date:  2021-09-13       Impact factor: 4.101

3.  Assessment of Telomerase Reverse Transcriptase Single Nucleotide Polymorphism in Sleep Bruxism.

Authors:  Piotr Macek; Mieszko Wieckiewicz; Rafal Poreba; Pawel Gac; Katarzyna Bogunia-Kubik; Marta Dratwa; Anna Wojakowska; Grzegorz Mazur; Helena Martynowicz
Journal:  J Clin Med       Date:  2022-01-20       Impact factor: 4.241

4.  The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders.

Authors:  Henry Loeffler-Wirth; Lydia Hopp; Maria Schmidt; Roksana Zakharyan; Arsen Arakelyan; Hans Binder
Journal:  Cells       Date:  2022-01-21       Impact factor: 6.600

Review 5.  CRISPR/Cas: A New Tool in the Research of Telomeres and Telomerase as Well as a Novel Form of Cancer Therapy.

Authors:  Mahendar Porika; Radhika Tippani; Gabriele Christine Saretzki
Journal:  Int J Mol Sci       Date:  2022-03-10       Impact factor: 5.923

  5 in total

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