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
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy