Mitochondria,
calcium and alphasynuclein
Chris
Project information
Lead researcher
Professor Christopher Miller
Location
Kings College London
Cost
£159,979 over 2 years
Start date
April 2014
Type of project
Project grant
Project code
G-1308
Project background
People with Parkinson’s don’t have enough of a chemical called dopamine because some
nerve cells in their brain have died. Although we don’t fully understand how or why this
happens, problems with the mitochondria – the tiny energy-producing batteries that power
our cells - are thought to be one of the key reasons nerve cells stop working and die.

Calcium is an important signaling molecule inside nerve cells. Mitochondria
receive calcium from another structure inside nerve cells called the ‘endoplasmic
reticulum’. When they receive calcium mitochondria make more energy. But too
much calcium is damaging so the flow of calcium has to be very carefully controlled.

The closer the endoplasmic reticulum and mitochondria are - the easier it is
for them to swap calcium. These structures are often physically connected by two
key proteins. This brings them closer together and enables calcium to flow more
easily between them.

Does alpha-synuclein affect these connections? Recent studies suggest that
calcium signalling between mitochondria and endoplasmic reticulum goes wrong in
Parkinson’s and this may be due to changes in the connections between them. A
rogue protein called alpha-synuclein may be to blame. Alpha-synuclein forms sticky
clumps, known as Lewy bodies, which clog up the affected nerve cells.
What the researchers are doing
Chris’s will work in partnership Dr Diane Hanger (also at Kings College London) to study
mitochondria in a range of cell and mouse models of Parkinson’s with different forms of the
alpha-synuclein protein.
Together they will use incredibly sensitive microscopes to investigate how alpha-synuclein
affects the protein connections between mitochondria and the endoplasmic reticulum.
They have already found some evidence that alpha-synuclein may disrupt the binding of
key proteins but need to study this in greater detail.
How the research will help people with Parkinson’s
If Chris and Diane succeed in finding more evidence that alpha-synuclein disrupts the
proteins that connect the endoplasmic reticulum and mitochondria, this will open up a
whole new avenue for developing drugs that preserve these essential connections.
They hope this research will lead to promising compounds that can be taken up by the
pharmaceutical industry and developed into new treatments for people with Parkinson’s.
-----------------------------------------------------------------------------------------------------------------------Find out more about our research, visit our website: parkinsons.org.uk/research
Or contact the Parkinson’s UK research team at:
Call
020 7963 9313
Email
[email protected]
Write
Parkinson’s UK, 215 Vauxhall Bridge Road, London SW1V 1EJ
Parkinson’s UK is the operating name of the Parkinson’s Disease Society of the United Kingdom. A company limited by
guarantee. Registered in England and Wales (948776). Registered office: 215 Vauxhall Bridge Road, London SW1V
1EJ. A charity registered in England and Wales (258197) and in Scotland (SC037554). © Parkinson’s UK, Nov 2012