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Telomerase activators improve motor function and protein degradation in a mouse model of Parkinson’s disease
International Conference on Parkinson’s, Huntington’s & Movement Disorders
April 17-18, 2019 | Frankfurt, Germany
Gabriele Saretzki and Tengfei Wan
Newcastle University, UK
Posters & Accepted Abstracts : J Brain Neurol
Abstract:
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. Analyzing levels of total, phosphorylated
and aggregated alpha synuclein 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 found a decrease
in poly-ubiquitinated proteins and the autophagy
receptor p62 and analyze 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
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, 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 87 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
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