Researchers at Sweden's Lund
University carried out a study on rats to reveal how Parkinson's disease (PD)
spreads throughout the brain.
In their experiments on rat models, they showed the method by
which misfolded proteins travel from sick PD cells to healthy cells. This
method has been used previously to explain the mad cow disease.
The breakthrough model developed by these researchers brings
them closer to developing a disease-modifying drug for Parkinson's disease.
The findings of this study have been published in
the latest Public Library of Science (PLoS) One.
According to Patrik Brundin M.D., Ph.D., working at the Van
Andel Research Institute (VARI), Sweden, "Parkinson's is the second most
common neurodegenerative disorder after Alzheimer's disease."
"A major unmet medical need is a therapy that slows disease
progression. We aim to better understand how Parkinson's pathology progresses
and thereby uncover novel molecular targets for disease-modifying
treatments," he added. Brundin is also the head author of this study.
Earlier studies have shown that a misfolded protein, called alpha-synuclein
protein, gradually appears in the healthy young neurons transplanted in the
Parkinson's patients' brain. This discovery pointed to a cell-to-cell protein
transfer-- a phenomenon which has been established through laboratory
experiments.
In the current study, the researchers focused on the dynamics
and were able to understand how the recipient healthy cell accepts the diseased
protein from the impaired cell by allowing the latter to pass through its outer
cell membrane, and how the transferred proteins attract the healthy proteins
within the host cells leading to "clumping" or abnormal folding within the
healthy cells.
"This is a cellular process likely to lead to the disease
process as Parkinson's progresses, and it spreads to an increasing number of
brain regions as the patient gets sicker," said Elodie Angot, lead
co-author of the study.
"In our experiments, we show a core of unhealthy human
alpha-synuclein protein surrounded by alpha-synuclein produced by the rat itself.
This indicates that this misfolded protein not only moves between cells but
also acts as a "seed" attracting proteins produced by the rat's brain
cells," said Jennifer Steiner, co- lead author.
What remains elusive is the mechanism by which the impaired
alpha-synuclein crosses the extracellular space to enter the cytoplasm of cells
and act as a template for naturally occurring alpha-synuclein within the cells
causing the latter to misfold. Further
studies are required to clarify this process.
The above study should help in the development of newer and more
effective drugs for Parkinson's disease.
Parkinson's disease is a neurological disorder
that affects motor function and cognitive skills. It currently affects more
than 1 per cent of people above 65 years of age.
Source-Medindia