The discovery, now published in the "FASEB Journal" has crucial implications for the study and treatment of those neurodegenerative illnesses - such as Parkinson’s, prion or Alzheimer’s diseases - which are known to result from aberrant protein interactions and deposits. In fact, the new technique, which the researchers test by studying the protein believed to be behind Parkinson’s disease, shows important potential not only to understand the mechanisms behind this type of diseases but also allows to observe, directly in the cells affected, the action of potential new treatments.
Parkinson’s disease (PD) is a progressive neurodegenerative disease characterised by increasing motor problems that can render the patient totally dependent of others for everyday tasks. The illness is believed to result from the loss of specific neural cells in an area in the brain - called substantia nigra - involved in motor function. These specific neuronal cells produce dopamine, a neurotransmitter used for the communication between the different parts of the brain involved in coordination and movement, and their death leads to interruption of the nervous signal and, ultimately, to the motor problems observed in PD patients.
Many neurodegenerative diseases, including PD, result from incorrectly folded proteins - all proteins have a specific shape/folding associated with their normal function – that either by becoming toxic, or by getting clumped together into insoluble aggregates, provoke the death of the brain cells in their surroundings. In the case of PD, the protein responsible for the pathology is believed to be alpha-synuclein, a brain protein of unknown function found in high quantities around the brain lesions of the subtantia nigra. Recently it has also been found that mutations or multiplications of the alpha-synuclein gene are responsible for some forms of Parkinson’s disease.
PD treatment and prevention is a medical priority in developed countries where the disease affects a striking 3% of the population above 65 years old, raising crucial financial issues especially as in these societies expectancy of life is steadily increasing and with it will also disease cases.
However, until now the understanding of this type of neurodegenerative diseases has been a very slow process due also to the lack of processes that could allow the observation of proteins directly inside the cell. But the development, by Jochen Klucken, Tiago F. Outeiro, Bradley T. Hyman and colleagues from the Massachusetts General Hospital, US and the University of Regensburg, Germany, of a technique called “Fluorescence Lifetime Imaging Microscopy” might change radically this. The new method consists in tagging the two ends of a protein with coloured dyes, which emit different energy specific wavelengths that can be read by a machine. The logic behind the technique is that the closer the two ends of the protein are (and so the two dyes), the higher is the interference between the two emitted wavelengths, allowing to infer if the protein has an open shape, is enrolled within itself or clotted together with other tagged proteins. This is crucial information as the same protein folded differently can have totally different effects/functions within the cell (it can even become toxic).
Using the new technique Klucken and colleagues studied alpha-synuclein in human cells and discovered a new aberrant interaction between different molecules of alpha-synuclein, which is probably involved in some forms of PD.
Even more interesting, the researchers were able to see inside the cell how the chaperone protein Hsp70 - chaperone proteins are molecules whose function is to assist other proteins achieving a proper folding – reverts alpha-synuclein toxicity.
In fact, although no cure for PD has been found so far, very promising work in animals and cells in laboratory has found that Hsp70 is capable of eliminating alpha-synuclein toxicity and so (theoretically at least) might help control the disease.
What the researchers now found was that Hsp70 opens alpha-synuclein misfolded structure allowing it to then revert to its normal (benign) shape. This result not only explains the mechanism behind Hsp70 protective effect, but proves that Fluorescence Lifetime Imaging Microscopy can be used to test new therapies in neurodegenerative diseases by directly accessing their effect inside the cells what is exciting news for both researchers and patients.
Piece researched and written by: Catarina Amorim (firstname.lastname@example.org)
Catarina Amorim | alfa
International team discovers novel Alzheimer's disease risk gene among Icelanders
24.10.2016 | Baylor College of Medicine
New bacteria groups, and stunning diversity, discovered underground
24.10.2016 | DOE/Lawrence Berkeley National Laboratory
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
24.10.2016 | Power and Electrical Engineering
24.10.2016 | Life Sciences
24.10.2016 | Life Sciences