New mechanisms found of cell death in neurodegenerative disorders

New mechanisms found of cell death in neurodegenerative


November 22, 2017


King’s College London


New mechanisms of cell death have now been discovered,
which may be involved in debilitating neurodegenerative disorders, such as
Alzheimer’s disease and Parkinson’s disease, report scientists.

Researchers at King’s College London have discovered new
mechanisms of cell death, which may be involved in debilitating
neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s

This novel research, published in Current Biology,
could lead to new therapeutic approaches for treating or delaying the
progression of neurodegenerative conditions that are currently incurable, if
the findings are expanded. Many current treatments for neurodegenerative
conditions actually aim to enhance cell clearance, which may worsen rather than
improve neurodegenerative symptoms, making the need for new treatment
strategies an urgent priority.

Approximately 10 million people in the UK live with a
neurological condition, with dementia alone estimated to cost the economy more
than £10.5 billion per year in health and social care. Neurodegenerative
conditions are characterised by a progressive loss of brain function, so that
patients start to lose control of their movement, balance, memory and speech —
similar to what happens when people have strong alcohol intoxication.

However, it is not currently known how or why these brain
cells lose function, particularly in the terminal stage of these illnesses.

Using two animal models of a degenerative neurological
disorder, the researchers were able to find a similar dysfunctional process
occurring in fruit flies and mice, as well as human cells, meaning that their
findings are likely to be replicated in human brains. Specifically, they found
that in this condition nerve cells in certain areas of the brain become stalled
and are no longer able to remove toxins or old and dysfunctional brain cells,
which is a naturally occurring process known as autophagy. Autophagy is
essentially how the brain breaks down cellular waste to elementary pieces,
which are then recycled and used to construct and renovate brain cells.

The persistent stall in autophagy means the nerve cells
are unable to ‘clean’ the brain and this results in a build up of toxins.
Essentially the cells become confused and begin pushing out essential inner
components rather than waste, leading to a loss of function and ultimately
their death.

This new insight into how nerve cells might die from
self-digestion has important implications for therapeutic approaches targeting
autophagy. While current treatments aim to enhance cell clearance, in this
study the authors were able to disrupt specific processes that interfere with
cell clearance.

Dr Olga Baron, first author from the Institute of
Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London,
said ‘Studies like ours, looking at rare genetic conditions, can be very
powerful in finding new mechanisms. We are currently looking into whether we
can replicate the same findings for other disorders where autophagy has been
shown to malfunction, like Alzheimer’s disease and motor neuron disease.’

Dr Manolis Fanto, IoPPN, King’s College London, senior
author of the study said ‘Autophagy is important for all degenerative
neurological conditions and what is emerging from our study is how the blockage
of autophagy kills nerve cells in a new way, not described before.’


Story Source:

Materials provided by King’s College
London. Note: Content may be edited for style and length.


Journal Reference:

1.            Manolis
Fanto et al. Stall in Canonical Autophagy-Lysosome Pathways Prompts
Nucleophagy-Based Nuclear Breakdown in Neurodegeneration. Current Biology,
November 2017 DOI: 10.1016/j.cub.2017.10.054