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The Role of Telomerase Protein TERT in Alzheimer's Disease and in Tau-Related Pathology In Vitro

Lookup NU author(s): Dr Alison Spilsbury, Dr Satomi Miwa, Professor Johannes Attems, Dr Gabriele Saretzki

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

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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