Pan European Networks - Horizon 2020 - page 55

during ageing, different neuronal cell populations just die and
neurodegenerative disorders subsequently develop.
This autophagy process is a key physiological process for the cellular
homeostasis, which applies also to proteins and their functions. In fact,
one of the really important hallmarks of ageing cells, in particular neuronal
cells but also for instance liver or skin cells, is the collection and
accumulation proteins that are malfunctioning and that subsequently form
protein aggregates.
For quite some time, cells can live with these intracellular aggregates,
but if these aggregates keep increasing, they are also recognised by this
autophagy process. The cells then try to get rid of these proteins, but
during ageing there are so many of these protein aggregates that the
cells can no longer cope with this huge load of them.
By identifying this particular feature, we have found a factor that is
essential for the onset of the autophagy process. We see this factor as
a potential prime target for modulation in order to stabilise autophagy
throughout a cell’s life but, in particular, aged cells; this is the focus of
our latest study.
How will the research help tackle neurodegenerative
diseases?
It is important to realise that there is currently no causal therapy to offer
to the millions of people that are developing Alzheimer’s in the EU and
worldwide. We need to encourage the pharmaceutical industry to
develop new therapies and promote alternative working hypotheses of
the cause of this disease, despite the financial implications. Ideally, we
need to develop a simple drug that targets the right cells at the right
time to prevent or treat the Alzheimer’s condition. However, in cases of
Alzheimer’s, the main research focus worldwide has so far been on
targeting the biochemistry of only two particular proteins (amyloid and
tau proteins), and despite 20 years of research little progress for therapy
has so far been made.
differences. Some years ago, my scientific
investigations uncovered that the process of
autophagy is also changing significantly while
the cells are ageing.
To put it simply, autophagy is a cell’s intrinsic
recycling programme – in Greek, ‘auto’
meaning ‘self’ and ‘phagy’ meaning ‘eating’.
Whenever a cell is under poor conditions,
meaning there is no nutritional support or there
is a low oxygen feed, then it has to maintain a
basic metabolism to survive during this time. In
these particular circumstances, the cell
degrades its own particles, proteins and other
properties in order to survive. This process is
called autophagy.
Autophagy can be carried out for quite some
time before the impact of an improving outside
nutritional environment gets better and the
cellular functions begin to run normally again.
In my lab, we found that through ageing, nerve
cells switch on particular efforts for increasing
autophagy and to improve the metabolic
turnover in neurons, for example.
Neurons are cells that do not divide and cannot
be replaced, so they optimise processes to
stabilise their function throughout their lifetime.
Most of the neurons are there when we are born
and they stay until we die. Autophagy is one
process that makes neurons stable but, as judged
from the high numbers of age-related brain
disorders, obviously not stable enough, because,
H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L
I S S U E S I X
55
N E U R O D E G E N E R AT I O N
The molecular interplay
of age-associated
biochemistry and
neurodegeneration
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