Now Dr. Li-Yang Chiang, Dr. Kate Poole and Professor Gary R. Lewin of the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch have discovered the causes underlying this disease.
Due to a genetic defect, individuals with EB cannot form laminin-332, a structural molecule of the skin that in healthy individuals inhibits the transduction of tactile stimuli and neuronal branching (Nature Neuroscience, doi: 10.1038/nn.2873)*. According to the findings of the MDC researchers, this explains why EB patients are more sensitive to touch and experience it as painful.
Even the slightest touch causes a stinging sensation like being stabbed with pins; the body is covered with blisters and the skin is inflamed in many places. Young patients with epidermolysis bullosa are often called “butterfly children” because their skin is as fragile as a butterfly’s wing. Because of the severe pain associated with the disease, EB sufferers hardly have any chance to lead a normal life. Even walking is a torment because of the pressure on the soles of the feet.
Due to a genetic defect, the patients’ outer skin layer (epidermis) separates from the underlying skin layer (dermis), and blisters (bullosa) are formed. EB patients are deficient in laminin-332, a structural molecule normally found between the skin cells in the extracellular matrix which serves as a kind of cellular “glue” between the two skin layers.
The new findings of the MDC researchers show that in healthy individuals, laminin-332 has other important functions as well: It inhibits touch transduction and prevents the branching of the sensory neurons that are receptive to tactile stimuli in the skin.
At their endings, sensory neurons have mechanosensitive ion channels. These are proteins in the cell membrane through which charged particles can flow into the cell in a controlled manner. Upon touch, pressure on the extracellular matrix actuates a tether mechanism on the ion channels, thus opening the channels and allowing the charged particles to flow through. This excites the neuron, thus enabling the stimulus to be perceived.
Furthermore, in the skin tissue of EB patients the MDC researchers found that sensory neurons showed much more branching than in the skin of healthy individuals. “From cell-culture experiments we know that laminin-332 inhibits neuronal branching. Without laminin-332 this inhibition does not take place. Presumably, this effect also contributes to the increased perception of tactile stimuli,” Professor Lewin said.
In further studies the researchers hope to find drug targets for therapy. However, much has already been achieved: “Because the causal mechanisms are now understood, we can focus on the patient’s pain situation and on administering more efficient pain therapies,” he added. “We recommend that in treating the disease, neurologists should be consulted in addition to dermatologists.*Laminin–332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons
Li-Yang Chiang1,5, Kate Poole1,5, Beatriz E. Oliveira2, Neuza Duarte1,Yinth Andrea Bernal Sierra1, Leena Bruckner-Tuderman3, Manuel Koch2, Jing Hu1,4 and Gary R. Lewin11Department of Neuroscience, Max Delbrück Center for Molecular Medicine and Charité Universitätsmedizin Berlin, Berlin, Germany. 2Institute for Oral and Musculoskeletal Biology, Center for Biochemistry, Department of Dermatology, and Center for Molecular Medicine Cologne, Medical Faculty, University of Cologne, Cologne, Germany.3Department of Dermatology and Freiburg Institute for Advanced Studies, School of Life Sciences LifeNet, University of Freiburg, Freiburg, Germany. 4Center for Integrative Neuroscience, Tübingen, Germany
5These authors contributed equally to this work.Barbara Bachtler
Barbara Bachtler | Max-Delbrück-Centrum
Researchers target protein that protects bacteria's DNA 'recipes'
21.08.2018 | University of Rochester
Protein interaction helps Yersinia cause disease
21.08.2018 | Schwedischer Forschungsrat - The Swedish Research Council
There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.
The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
21.08.2018 | Ecology, The Environment and Conservation
21.08.2018 | Life Sciences
21.08.2018 | Power and Electrical Engineering