Telomerase gene therapy ameliorates the effects of neurodegeneration associated to short telomeres in mice
Whittemore, Kurt (Centro Nacional de Investigaciones Oncológicas)
Derevyanko, Aksinya (Centro Nacional de Investigaciones Oncológicas)
Martínez, Paula (Centro Nacional de Investigaciones Oncológicas)
Serrano, Rosa (Centro Nacional de Investigaciones Oncológicas)
Pumarola i Batlle, Martí (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Blasco, María A. (Centro Nacional de Investigaciones Oncológicas)

Fecha:	2019
Resumen:	Neurodegenerative diseases associated with old age such as Alzheimer's disease present major problems for society, and they currently have no cure. The telomere protective caps at the ends of chromosomes shorten with age, and when they become critically short, they can induce a persistent DNA damage response at chromosome ends, triggering secondary cellular responses such as cell death and cellular senescence. Mice and humans with very short telomeres owing to telomerase deficiencies have an earlier onset of pathologies associated with loss of the regenerative capacity of tissues. However, the effects of short telomeres in very low proliferative tissues such as the brain have not been thoroughly investigated. Here, we describe a mouse model of neurodegeneration owing to presence of short telomeres in the brain as the consequence of telomerase deficiency. Interestingly, we find similar signs of neurodegeneration in very old mice as the consequence of physiological mouse aging. Next, we demonstrate that delivery of telomerase gene therapy to the brain of these mice results in amelioration of some of these neurodegeneration phenotypes. These findings suggest that short telomeres contribute to neurodegeneration diseases with aging and that telomerase activation may have a therapeutic value in these diseases.
Ayudas:	Ministerio de Economía y Competitividad SAF2013-45111-R Ministerio de Economía y Competitividad SAF2015-72455-EXP
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Telomerase ; Gene therapy ; Neurodegeneration ; TERT
Publicado en:	Aging (Albany NY), Vol. 11 (may 2019) , p. 2916-2948, ISSN 1945-4589

DOI: 10.18632/aging.101982
PMID: 31140977

33 p, 9.6 MB

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