![]() Oehler B, Kistner K, Martin C, Schiller J, Mayer R, Mohammadi M, Sauer RS, Filipovic MR, Nieto FR, Kloka J, Pflücke D, Hill K, Schaefer M, Malcangio M, Reeh PW, Brack A, Blum R, Rittner HL (2017) On the objectivity, reliability, and validity of deep learning enabled bioimage analyses. Segebarth D, Griebel M, Stein N, R von Collenberg C, Martin C, Fiedler D, Comeras LB, Sah A, Schoeffler V, Lüffe T, Dürr A, Gupta R, Sasi M, Lillesaar C, Lange MD, Tasan RO, Singewald N, Pape HC, Flath CM, Blum R. Pain Control by Targeting Oxidized Phospholipids: Functions, Mechanisms, Perspectives.įront Endocrinol (Lausanne), 2021 Jan 25 11: 613868. Oehler B, Brack A, Blum R, Rittner H (2021) University Hospital Würzburg Members of the team In this project, we will also develop and test mouse models to study pain relief and resolution for other projects such as P6. If this can be confirmed, therapeutic strategies that promote natural, endogenous mechanisms of pain resolution could be tested. Preliminary data already indicate that the cellular cholesterol transporter ABCA1, as a key element in the regulation of apolipoprotein A1 and HDL, plays a central role in pain development and pain resolution. In a translational approach, the correlation between pain relief and serum ApoA/ HDL cholesterol profiles will be investigated in patients with complex regional pain syndrome ( CRPS) and chronic postoperative groin pain. To validate the hypotheses, inducible, cell type-specific ABCA1 knockout mice will be developed - animals in which ABCA1-encoding genes in pain receptors have been selectively inactivated. Furthermore, we investigate animal models carrying a chronic nerve ligation to find out how cell profiles, apolipoproteins and ABC transporters change quantitatively and qualitatively during the development and resolution of neuropathic pain. Here, the focus is on methods that record the excitability of the pain receptors. The mode of action and principles of lipid proteins will be investigated using cultured ‘pain receptors’, so-called nociceptors. The quantitative and qualitative content of cholesterol and phospholipids in the cell membrane influences the activity of ion channels and thus affects pain stimuli. ![]() ABCA1 transports cholesterol and phospholipids from inside the cell to the cell surface, where they are partly incorporated into the cell membrane or become part of HDL-like particles. ApoA1 is an important component of high- density lipoprotein ( HDL) and holds the HDL molecule and its components together. Project 9 of ResolvePAIN will focus on the function of apolipoprotein A1 (ApoA1) and the transport protein ABCA1 in pain development and resolution of pain. Radiation Emergency Centers Show Overview ».Interdisciplinary Cleft Lip and Palate Center.Interdisciplinary Center for Thoracic Diseases Mainfranken (iTZM).Interdisciplinary Center for Palliative Medicine.Würzburg Center for Neurofibromatoses (WCNF).Interdisciplinary Amyloidosis Center of Northern Bavaria.FaZit Fabry Center for interdisciplinary therapy.Christiane Herzog Center for Cystic Fibrosis Lower Franconia.Center for rare Red Cell and Platelet Disorders.Center for rare pediatric bone diseases.Center for rare Endocrine Disorders (CRET).Center for Primary Immunodeficiencies (ZIN).Center for Inherited Blood Cell Disorders.Center for Genetic Cardiovascular Diseases.Center for Achalasia and other Esophageal Motility Disorders.We also discuss the impact and limitations of model systems and structure prediction methods in understanding human ABC transporters and discuss current challenges and future research directions.Įxpected final online publication date for the Annual Review of Biophysics, Volume 52 is May 2023. Here we review this recent progress, highlighting the physiological relevance of human ABC transporters and mechanistic insights gleaned from their direct structure determination. As a result, experimentally determined structures of multiple members of each of the five families of ABC transporters in humans are now available. Over the last decade, advances in structural biology have vastly expanded our mechanistic understanding of human ABC transporter function, revealing details of their molecular arrangement, regulation, and interactions, facilitated in large part by advances in cryo-EM that have rendered hitherto inaccessible targets amenable to high-resolution structural analysis. Of these genes, 44 (in five distinct families) encode for membrane transporters, of which several are involved in drug resistance and disease pathways resulting from transporter dysfunction. Humans have 48 ABC genes organized into seven distinct families. ABC transporters are essential for cellular physiology.
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