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allied
academies
Brain Disorders and Therapeutics
Mental Heal th and Psychology
5th International Conference on
Joint Event
&
Journal of Brain and Neurology| Volume: 2
November 05-06, 2018 | Edinburgh, Scotland
Telomerase activators improvemotor function and protein degradation in amousemodel of Parkinson’s
disease (PD)
Gabriele Saretzki and Tengfei Wan
The Ageing Biology Centre, Institute for Cell and Molecular Biosciences, UK
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. TERT protein persist in adult
neuronswhile telomerase activity is downregulatedearly during
development (Ishaq et al., 2016). We recently demonstrated
increased mitochondrial TERT protein in hippocampal neurons
from Alzheimer’s disease brains and mutual exclusion of
pathological tau and TERT. 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 such as PD.
OraltreatmentofPDmodelmiceoverexpressinghumanwild-type
alpha-synuclein (line D, Masliah et al., 2000) with 2 telomerase
activators resulted in increased TERT expression in brain and
ameliorationofPDsymptomsbysignificantly improvingbalance,
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 (Im et al., 2016, Ali et al., 2016).
Accordingly, we found inour preliminary data adecrease inpoly-
ubiquitinated proteins and the autophagy receptor p62 and
analysetheinvolvementofthesedegradationpathwayscurrently.
Thus, our results suggest that telomerase activators might
form novel treatment options for better degradation of toxic
proteins in neurodegenerative diseases such as PD and AD.
Speaker Biography
Gabriele has completed her PhD 1990 at Humboldt University Berlin and performed
most of her postdoctoral studies at the Institute for Ageing and 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 and mitochondria. 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 84 papers in peer-reviewed journals and is an editorial boardmember of BMC Biology,
PloS One and Oxidative Medicine and longevity.
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