The FINANCIAL — The stability of a particular protein in the body could influence the onset of neurodegenerative disease, Scientists at the University of Liverpool and the University of Nagoya, Japan, have found.
Mutations to a DNA binding protein, called TDP-43, are linked with motor neurone disease and a number of other of neurodegenearative diseases, including Alzheimer’s and Guam-Parkinson’s Dementia.
TDP-43 binds to large molecules, called ribonucleic acid (RNA), which is at the heart of the process that allows DNA to be read and used for the manufacture of proteins. Scientists have now shown that mutations in TDP-43 can occur that leads to the protein breaking down at a slower rate than normal, resulting in an accumulation of the protein in the cells.
It is not known why these mutations occur, but it is thought that this process can influence the age at which motor neurone disease patients first show symptoms of the disease.
The slower rate of degradation means that TDP-43 accumulates in the cells and could ultimately lead to neurone death by changing the delicate metabolism of these fragile cells, triggering the onset of disease, according to University of Liverpool.
“These changes to TDP-43 are unusual because most proteins involved in neurodegeneration are unstable. This is the case in Alzheimer’s, Parkinson’s and Huntington’s diseases and motor neurone disease, which results from mutations in another protein, called superoxide dismutase,” Biochemist, Dr Gareth Wright, at University’s Molecular Biophysics group in Institute of Integrative Biology, said.
The findings open avenues for further research including development of drugs that decrease TDP-43 stability and accelerate its degradation to prevent accumulation in cells.
“The fact that TDP-43 is associated with many neurodegenerative diseases warranted investigation. We were able to discover the protein’s structure, half-life, aggregation propensity and stability. We identified that TDP-43’s cellular longevity is due to higher thermal stability and resistance to unfolding,” Dr James Austin, who completed his PhD on the research, said.
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