Van Andel Institute announces that researchers at Lund University in Sweden have published a study detailing how Parkinson’s disease spreads through the brain. Experiments in rat models uncover a process previously used to explain mad cow disease, in which misfolded proteins travel from sick to healthy cells. This model has never before been identified so clearly in a living organism, and the breakthrough brings researchers one step closer to a disease-modifying drug for Parkinson’s.
“Parkinson’s is the second most common neurodegenerative disorder after Alzheimer’s disease,” said Patrik Brundin M.D., Ph.D., Jay Van Andel Endowed Chair in Parkinson’s Research at Van Andel Research Institute (VARI), Head of the Neuronal Survival Unit at Lund University and senior author of the study. “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.”
Previous research demonstrates that a misfolded protein known as alpha-synuclein protein gradually appears in healthy young neurons transplanted to the brains of Parkinson’s patients. This discovery gave rise to the group’s hypothesis of cell-to-cell protein transfer, which has since been demonstrated in laboratory experiments.
In the current study, published this week in the Public Library of Science (PLoS) One, researchers for the first time were able to follow events in the recipient cell as it accepts the diseased protein by allowing it to pass its outer cell membrane. The experiments also show how the transferred proteins attract proteins in the host cell leading to abnormal folding or “clumping” inside the 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, Ph.D., of Lund University’s Neuronal Survival Unit, and 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, Ph.D., of Lund University and Van Andel Institute’s Center for Neurodegenerative Science, the study’s other lead author.
These findings are consistent with results from previous laboratory cell models and for the first time extend this observation into a living organism. However, it remains unclear exactly how alpha-synuclein gains access from the extracellular space to the cytoplasm of cells to act as a template for naturally occurring alpha-synuclein, causing the naturally-occurring protein to, in turn, misfold. Further studies are needed to clarify this important step in the process.
The discovery does not reveal the root of Parkinson’s disease, but in conjunction with disease models developed by Lund University researchers and others, could enable scientists to develop new drug targets aimed at mitigating or slowing the effects of the disease, which currently strikes more than 1% of people over the age of 65.
Archive for June 27th, 2012
Posted by Xeno on June 27, 2012
Posted by Xeno on June 27, 2012
Although there have been about 800 extra-solar planets discovered so far in our galaxy, the precise masses of the majority of them are still unknown, as the most-common planet-finding technique provides only a general idea of an object’s mass. Previously, the only way to determine a planet’s exact mass was if it transits—has an orbit that periodically eclipses that of its host star. Former Carnegie scientist Mercedes López-Morales has, for the first time, determined the mass of a non-transiting planet. The work is published by Astrophysical Journal Letters.
Knowing a body’s mass is essential first to confirm it is a planet and if so, to determine whether it is rocky and possibly habitable or large and gassy. Until now, only the masses of transiting planets have been measured. Transiting planets are also the only type of extra-solar objects on which atmospheres have been detected.
López-Morales, along with her colleagues Florian Rodler and Ignasi Ribas of the Institute of Space Sciences, ICE (CSIC-IEEC, in Barcelona, Spain) measured the exact mass of a non-transiting planet. They did this using a new method that involves studying the carbon monoxide signature of the planet’s atmosphere—detecting, in the process, the atmosphere of this non-transiting planet.
The planet is called Tau Boo b, located in the constellation of Bootes, and it orbits a star about 50 light years from Earth that’s bright enough to be visible to the naked eye. The planet is similar in size to Jupiter and is so close to its star (only 8 stellar radii), that a year for this planet asts only 3.3 Earth days. Furthermore, its surface temperature reaches 1,500 ° C, making it inhospitable to life.
Discovered in 1996, Tau Boo b was one of the first planets originally detected by the radial velocity method. This planet does not transit, but its presence and characteristics were initially determined by the wobble of its host star. This technique only provides a rough indication of a detected planet’s mass.
In June 2011, López-Morales’ team conducted five hours of observations at near infrared wavelength (2.3 microns). They obtained data from the high-resolution spectrograph CRIRES, an instrument mounted on one of the four 8.2m Very Large Telescopes (VLT) of the European Southern Observatory (ESO) in Chile.
The observations and subsequent data analysis revealed the presence of carbon monoxide in the planet’s atmosphere. In addition, by studying the planet’s orbital motion through the displacement of spectral lines of carbon monoxide, the team was able to calculate its exact mass—5.6 times Jupiter—a first using this particular method, and also a first for a non-transiting planet.
An independent study conducted by researchers at the University of Leiden in the Netherlands obtained a similar result for the same planetary system, confirming the potential of this technique.
“This method represents a strong advance in the field of exoplanets,” said Lopez-Morales. “It opens a new path to determine masses of exoplanets and the composition of their atmospheres” …