Unique protein structures could hold the key to treatment for
Parkinson's disease

Date:
August 20, 2020
Source:
University of Bath
Summary:
Scientists have discovered a series of protein structures that
are thought to be highly relevant to the onset of Parkinson's
disease. It is hoped that further analysis of these structures
will open up a new avenue for potential treatment for a disease
that is the fastest growing neurological condition in the world,
with no cure currently available.



FULL STORY ========================================================================== Scientists at the University Bath in the UK have discovered a series of
protein structures that are thought to be highly relevant to the onset of Parkinson's disease. It is hoped that further analysis of these structures
will open up a new avenue for potential treatment for a disease that is
the fastest growing neurological condition in the world, with no cure
currently available.


========================================================================== According to Parkinson's UK, more than 1 million people in the UK are
affected by the disease -- either by living with the condition, or as a
friend, colleague, or family member of someone who is. Latest estimates
show that in 2020, around 145,000 people live with a Parkinson's diagnosis
in the UK.

The disease is characterised by a specific protein 'misfolding',
where it becomes distorted and then malfunctions. The protein which
researchers at Bath have studied -- alpha-synuclein (?S) -- is abundant
in all human brains. After misfolding, it accumulates in large masses,
known as Lewy bodies. These masses consist of slender ?S fibres that are
toxic to dopamine-producing brain cells, causing them to die. It is this
drop in dopamine that triggers the symptoms of Parkinson's Disease.

There has been much research into ?S structure and the role it plays in Parkinson's, however virtually all studies have taken place in laboratory
test tubes, where the protein is purified from bacteria and studied
in isolation.

Research of this kind often overlooks the fact that in the living
brain, ?S fibres form in the presence of 'phospholipids' -- large fatty substances that make up cell membranes and play an essential role in
living cells, both in their structure and metabolism.

In the new Bath study, published in Nature Partner Journal -- Parkinson's disease, Professor Jody Mason and his team from the Department of
Biology & Biochemistry examined how ?S misfolds in the presence of phospholipids. They discovered a series of misfolded protein structures
that have never been observed before. These ?S fibres were larger than
any previously reported and took on a striking variety of shapes. Some
formed flat ribbons, others appeared as long, wave-like helices, while
others still were more compact and bulkier.

The Bath researchers hope their discovery will mark the start of a new
era in Parkinson's research. Their work lays the foundation for detailed analysis of misfolded ?S fibres. Once the structure of these fibres is
better understood, scientists will be able to investigate which versions
are disease-causing and which are not. From here, they will be able
to test drugs against pathogenic forms. This will constitute a major
step forward in finding a cure for Parkinson's and other neurological conditions.

"We know that these misfolded proteins are heavily implicated
in Parkinson's disease," said Professor Mason. "What's more,
alpha-synuclein is known to be important in neurotransmission and in
cell signalling. Given its interaction with brain cell membranes, the
discovery of these structures in the presence of phospholipids may have far-reaching implications in our quest to find a disease-causing form
of the protein." The research charity Parkinson's UK has invested over
-L-3.5 million in understanding the role played in the brain by ?S. It recognises that unlocking the secrets of this protein could hold the
key to finding a cure for the condition.

Dr Beckie Port, research manager at Parkinson's UK, said: "Alpha-synuclein
is known to form different structures, and researchers have become
increasingly interested in which forms of the protein may be toxic, and
linked to the spread and loss of brain cells in Parkinson's -- this is essential in order to develop treatments that target the right form of
the protein.

"By advancing our understanding of the different structures of the protein
that are likely to be present inside brain cells, this University of
Bath study helps pave the way for developing treatments that may one
day stop the progression of Parkinson's."

========================================================================== Story Source: Materials provided by University_of_Bath. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Richard M. Meade, Robert J. Williams, Jody M. Mason. A series
of helical
a-synuclein fibril polymorphs are populated in the presence
of lipid vesicles. npj Parkinson's Disease, 2020; 6 (1) DOI:
10.1038/s41531-020- 00122-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200820102422.htm

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