Parkinson's disease is induced by alpha-synuclein strains shaped like 'cylinders' (c) Shutterstock
10 June 2015
Several
neurodegenerative disorders are caused by aggregates of a single protein known
as alpha-synuclein. In collaboration with CNRS and the University of Antwerp,
KU Leuven neurobiologists have discovered that the shape of these aggregates –
‘cylinders’ or ‘ribbons’ – determines whether a patient develops Parkinson’s
disease or Multiple System Atrophy, respectively.
Typical of
neurodegenerative disorders is the disrupted
communication between brain cells
together with a loss of
cells in specific brain regions. For some brain
diseases this phenomenon is linked to a
protein known as alpha-synuclein. The
exact function of this protein remains unclear, but it
may play a role in the
communication between brain cells. However, in the case of specific
diseases,
including Parkinson’s disease, Multiple System Atrophy (MSA), and dementia
with Lewy bodies (DLB), this protein forms aggregates that cause neurodegeneration.
“When alpha-synuclein aggregates
accumulate within a brain cell, they interfere with the
normal functioning of
the cell. The protein aggregates disrupt the communication between
brain cells,
resulting in cell death. Up to now, nobody understood how aggregates of this
single protein could induce different pathologies,” says Professor Veerle Baekelandt from
the Research Group for
Neurobiology and Gene Therapy.
“You could compare it to the
construction of a house,” doctoral researcher Wouter
Peelaerts explains. “With the same building blocks
– in this case the alpha-synuclein
protein – you can create many different
structures. In 2013, Professor Ronald Melki and his
colleagues from CNRS
isolated several forms of fibres called ‘strains’. The two most
important
strains were cylinder-shaped fibres reminiscent of spaghetti and broad ribbons
that resemble linguini. We injected these fibres separately into the brain and
blood stream of
rats. We noticed that the rats developed different symptoms:
while the ‘cylinders’ induced
Parkinson’s disease, the ‘ribbons’ caused MSA
symptoms.” This clearly demonstrates that
distinct diseases result from
alpha-synuclein fibres that are structurally different.
“We are gaining more insight into the
differences between the diseases," Baekelandt
concludes. "But we
suspect that more fibres with different shapes and effects are waiting to
be
discovered, apart from the two that we examined in this study. In any case, our
findings
open up possibilities for the development of new treatments. A drug
that counteracts the
development of aggregates could be used to treat a whole
range of brain diseases.”
http://www.kuleuven.be/english/news/2015/single-protein-causes-parkinsons-disease-and-multiple-system-atrophy
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