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July 01-02, 2019 | Paris, France
Brain Disorders and Therapeutics
6
th
International Conference on
Page 12
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Journal of Brain and Neurology | Volume: 03
Gabriele Saretzki
Newcastle University, UK
Telomerase activators improve motor function and protein
degradation in a mouse model of Parkinson’s Disease (PD)
W
hile 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.
Speaker Biography
Gabriele Saretzki has completed her PhD in 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, 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:
gabriele.saretzki@ncl.ac.uk