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Gabriele Saretzki
Newcastle University, UK
Keynote: J Neurol Clin Neurosci
While telomerase maintains telomeres in dividing cells,
its protein component TERT (Telomerase reverse
transcriptase) has various non-canonical functions such as
localisation to mitochondria resulting in decreased oxidative
stress, apoptosis and DNA damage. The TERT protein persists
in adult neurons while telomerase activity is downregulated
early during development (Ishaq et al., 2016).
We recently demonstrated increased mitochondrial TERT
protein in hippocampal neurons from Alzheimer�s disease
(AD) brains and mutual exclusion of pathological tau and TERT
protein. Transduction of mutated tau into cultivated neurons
confirmed that TERT decreases mitochondrial oxidative stress
and lipid oxidation (Spilsbury et al., 2015). Mitochondrial
dysfunction is also involved in the development of other
neurodegenerative diseases.
Treatment of PD model mice (Masliah et al., 2000)
overexpressing human wild-type alpha-synuclein with 2
telomerase activators (TA Science Inc., USA) resulted in
increased TERT expression in brain and amelioration of PD
symptoms by significantly improving balance, gait and motor
function as well as mitochondrial function. Analysing levels
of total, phosphorylated and aggregated alpha-synuclein we
found a substantial decrease of all these protein forms in
the hippocampus and neocortex suggesting a better protein
degradation after telomerase activator treatment. Interaction
of TERT with proteasomal and autophagy pathways has
been described recently. Accordingly, we have preliminary
data showing a decrease in poly-ubiquitinated proteins and
the autophagy receptor p62 and analyse the involvement of
these degradation pathways currently.
Thus, our results suggest that telomerase activators might
form a novel treatment option for better degradation of toxic
proteins in neurodegenerative diseases such as PD and AD.
Gabriele Saretzki has completed her PhD 1990 at Humboldt University Berlin and performed most of her postdoctoral studies at the Institute for Ageing. Health in Newcastle upon Tyne (UK) where she is a Lecturer in Ageing Research since 2002. Her main interests are telomeres, telomerase, senescence, ageing, oxidative stress, mitochondria, stem cells and brain. She has pioneered work on non-canonical functions of the telomerase protein TERT shifting her focus recently to brain ageing and neurodegenerative diseases. She has published more than 88 papers in peer-reviewed journals and is an editorial board member of BMC Biology, PloS One and Oxidative Medicine and longevity.
E-mail: gabriele.saretzki@ncl.ac.uk
+44 73620 49920
