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Lookup NU author(s): Dr Alison Spilsbury, Dr Satomi Miwa, Professor Johannes Attems, Dr Gabriele Saretzki
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The telomerase reverse transcriptase protein TER Thas recently been demonstrated to have a variety of functions both in vitro and in vivo, which are distinct from its canonical role in telomere extension. In different cellular systems, TERT protein has been shown to be protective through its interaction with mitochondria. TERT has previously been found in rodent neurons, and we hypothesize that it might have a protective function in adult human brain. Here, we investigated the expression of TERT at different stages of Alzheimer's disease pathology (Braak Stages I-VI) in situ and the ability of TERT to protect against oxidative damage in an in vitro model of tau pathology. Our data reveal that TERT is expressed in vitro in mouse neurons and microglia, and in vivo in the cytoplasm of mature human hippocampal neurons and activated microglia, but is absent from astrocytes. Intriguingly, hippocampal neurons expressing TERT did not contain hyperphosphorylated tau. Vice versa, neurons that expressed high levels of pathological tau did not appear to express TERT protein. TERT protein colocalized with mitochondria in the hippocampus of Alzheimer's disease brains (Braak Stage VI), as well as in cultured neurons under conditions of oxidative stress. Our in vitro data suggest that the absence of TERT increases ROS generation and oxidative damage in neurons induced by pathological tau. Together, our findings suggest that TERT protein persists in neurons of the adult human brain, where it may have a protective role against tau pathology.
Author(s): Spilsbury A, Miwa S, Attems J, Saretzki G
Publication type: Article
Publication status: Published
Journal: Journal of Neuroscience
Year: 2015
Volume: 35
Issue: 4
Pages: 1659-1674
Print publication date: 28/01/2015
Acceptance date: 11/12/2014
Date deposited: 10/08/2015
ISSN (print): 0270-6474
ISSN (electronic): 1529-2401
Publisher: Society for Neuroscience
URL: http://dx.doi.org/10.1523/JNEUROSCI.2925-14.2015
DOI: 10.1523/JNEUROSCI.2925-14.2015
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