Contributions to Max Planck Society Yearbooks
2018 Sereda, Michael W.; Fledrich, Robert; Prukop, Thomas; Stassart, Ruth; Nave, Klaus-ArminCharcot-Marie-Tooth disease (CMT) is the most common hereditary neuropathy of the peripheral nervous system. So far no treatment is available. Using transgenic animal models, we have developed new therapeutic approaches which are currently being translated to humans, thus creating new therapeutic options for approximately 1.5 million affected CMT patients worldwide.
2017 Brose, Nils; Sigler, Albrecht; Imig, Cordelia; Altas, Bekir; Kawabe, Hiroshi; Cooper, Benjamin; Kwon, Hyung-Bae; Rhee, Jeong-Seop
According to the current dogma in neuroscience, neurons in the brain must communicate actively with each other to establish functional networks. Recent results now demonstrate that neurons in a brain region that is critically involved in learning and memory processes can connect and form structurally normal networks without active signal transmission at their synaptic contact points.
2016 Stühmer, Walter; Pardo, Luis A.Ion channels are membrane proteins that regulate cellular processes by transmitting signals across membranes. Thus it is not surprising that they are also involved in cancer. In this respect, Kv10.1 is the most intensively studied potassium channel. It is overexpressed in over 70% of all cancer forms, and its expression level is up- and down-regulated during the cell cycle. This genetic regulation happens at the centre of signalling cascades involved in cancer and cell division regulation. Consequently, Kv10.1 represents a novel target for cancer treatment.
2015 Schmidt, Manuela
Pain is a major symptom of many diseases and the worldwide number one reason for people to seek medical assistance. While acute pain subserves protective functions, chronic pain conditions present a big challenge to patients and clinicians alike. In light of these difficulties, the identification of proteins specifically involved in chronic pain states would open new avenues for designing selective and efficient therapeutical interventions.
2014 Gütig, Robert
The question how the almost 100 billion nerve cells of the human brain represent and process sensory stimuli and thoughts is one of the most fascinating challenges in neuroscience. Contrary to common belief that nerve cells encode information by the rate of action potential firing, a growing number of experimental and theoretical accounts is strengthening alternative hypotheses that neural codes could be more refined and for instance incorporate also temporal intervals between action potentials of different neurons.
2013 Nave, Klaus-ArminOne of the most spectacular interactions of cells in the central nervous system is the myelination of axons by oligodendrocytes, which serves the rapid impulse propagation. Max Planck scientists have discovered a novel function of oligodendrocytes in the metabolic support of myelinated axons. Genetic evidence suggests that oligodendrocytes are glycolytic cells that release lactate as an energy-rich metabolite. Loss of this trophic function of oligodendrocytes may play a critical role in inherited and acquired myelin diseases.
2012 Kannan, Madhuvanthi; Schwedhelm-Domeyer, Nicola; Stegmüller, JudithAxon growth is an essential event in the developing central nervous system. While a large body of evidence characterizes extrinsic mechanisms, there is little knowledge about intrinsic signaling pathways of axon growth regulation. The E3 ligase Cdh1-APC has been identified as a novel intrinsic inhibitor of axon growth. Thus, the research focuses on the elucidation of the Cdh1-APC signaling pathway.
2011 Aggarwal, Shweta; Simons, MikaelMyelin is an electrical insulator essential for the rapid conduction of nerve impulses in the central nervous system. In order to do so, myelin requires a unique lipid and protein composition. Recent findings demonstrate that oligodendrocytes generate a barrier that functions as a physical filter to form the lipid-rich myelin membrane sheets. Myelin basic protein establishes this molecular sieve and restricts the diffusion of proteins into myelin. This mechanism generates the anisotropic membrane organization of oligodendrocytes that facilitates the assembly of highly insulating membranes.
2010 Hartung, Franziska; Stühmer, Walter; Pardo, Luis A.Tumor therapy relies on tumor markers for the specific destruction of tumor cells. Max Planck scientists discovered and characterized a potassium channel (Eag1) as a new tumor marker [1, 2]. This channel was used to bind a cell-death inducing mediator TRAIL to cancer cells. In cell culture they could show suicide activation, specifically in the Eag1 positive prostate cancer cells. Cell death could also be induced in neighboring Eag1 negative prostate cancer cells, whereas normal prostate cells were unaffected.
2009 Varoqueaux, FrédériqueFast neuronal communication in the central nervous system takes place at excitatory and inhibitory synapses. The accuracy and efficiency of synaptic transmission rely on the proper assembly of specific adhesion, scaffold, receptor, and signaling proteins. Postsynaptic adhesion proteins of the Neuroligin family were identified as key regulators of this assembly process at excitatory glutamatergic synapses. Recent studies showed that Neuroligins also regulate the formation of GABAergic and glycinergic synapses. Thus, Neuroligins are essential regulators of synaptogenesis at all fast synapses in the central nervous system.
2008 Ehrenreich, Hannelore; Bartels, Claudia; Begemann, Martin; Krampe, HenningScientists at the MPI for Experimental Medicine developed a mouse model where they induce neurodegeneration in juvenile mice by stereotactic unilateral parietal cortical cryolesion. This procedure causes non-gliotic neurodegeneration and changes in plasticity comparable to schizophrenia which are all prevented by erythropoietin (EPO). Similarly, amelioration of cognition and deceleration of brain atrophy in schizophrenic patients is seen after a 12-week EPO treatment. Mechanistic explanation of cognitive improvement is delivered by EPO-induced increase in long term potentiation, an indicator of learning and memory.
An experimental strategy for the global gene expression profiling of fluorescently labeled cell types in the adult mouse brain2006 Rossner, Moritz'Genechips' are powerful tools to study simultaneously the expression of essentially all genes. The enormous cellular complexity of the mammalian brain, however, is a major obstacle for sensitive gene expression profiling, for example when analyzing mouse models of neurological diseases. Scientist at the MPI for Experimental Medicine have solved this problem by labeling individual cells in transgenic mice that express a nuclear fluorescent protein. Using laser-directed microdissection, expression profiles can be obtained from as few as 100 isolated neurons.
2005 Miquelajauregui, Amaya; Tarabykin, VictorSIP1 is a transcription factor that has been implicated in the genesis of Mowat-Wilson syndrome – a disease that affects normal brain development in humans. In order to uncover molecular mechanisms of Sip1 gene action scientists of the MPI for experimental medicine created a mutant mouse as a model for the syndrome. In this mouse Sip1 gene was inactivated in the cerebral cortex only, while in other organs it remained intact. The mutant mice showed loss of the entire hippocampus, which was based on elevated cell death and decreased proliferation during development.
2004 Krampe, Henning; Stawicki, Sabina; Wagner, Thilo; Ribbe, Katja; El Kordi, Ahmed; Niehaus, Silja; Ehrenreich, HanneloreOLITA, the Outpatient Longterm Intensive Therapy for Alcoholics, was developed as a comprehensive research project in 1993. This paper reports on the results of the OLITA project and its future perspectives. In summer 2003, the monocentric pilot study in Göttingen was completed successfully after ten years and the enrollment of 180 patients. More than 50% of the patients remained abstinent during a follow-up of up to seven years after termination of therapy. The unemployment rate declined from 58% to 22%, comorbid psychiatric disorders decreased from 60% to 13%. An ongoing video-based prospective longitudinal study investigates the therapeutic processes associated with this success. At present, a multicenter trial for the translation of OLITA using the franchising approach is initiated.
2003 Terlau, HeinrichIon channels are membrane bound proteins that are involved in a great variety of different physiological processes like electrical excitability of cells or absorption and secretions within the epithelia. Ion channels can be activated by different signals and malfunction of these proteines can lead to diseases. Several hereditary diseases like cystic fibrosis or special forms of epilepsy, deafness or heart arrhythmia are known to be correlated with mutations of certain ion channels. Due to their special role in different areas of cellular function ion channels are "popular" targets of biological active substances from different venomous organisms. The laboratory of Heinrich Terlau tries to understand how these substances interact with their target molecules. The focus of their research is the investigation of the mechanism of action of toxins from cone snails interacting with voltage gated ion channels. The aim is to establish new tools for studying the physiological role of a given target and to create the basis for a potential pharmacological or even clinical use of these substances.