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
Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society
New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
23.02.2017 | Physics and Astronomy
23.02.2017 | Earth Sciences
23.02.2017 | Life Sciences