Institute for interdisciplinary pharmacology -
Prof. Dr. Walter E. Müller

Expertise

Neurodegeneration und neuroprotective drugs
Oxidative stress und anti-oxidants
Neuropsychopharmacology

Resources and Abilities

Apoptosis and Necrosis: DNA-Fragmentation [FACS]; Nucleosom-ELISA, TUNEL-Staining [Fluorescence-microscope]; MTT-, LDH-, ATP-Assay (IN-VITRO-TEST SYSTEMS)
Immunology: Determination of specific markers (CD-3, CD-4, CD-8, IL-2, IL-6 a.o.) [FACS], Expressions of Bcl-2, Bax a.o. (IN-VITRO-TEST SYSTEMS)
Oxidative Stress: Enzyme activities (SOD, GPx a.o.); GSH-Levels; MDA- und HNE-Levels; Antioxidative Capacity (TEAC), Hydroperoxide Levels, Haemoglobin-Degradation-Assay, Guaiacol-Oxidation-Assay (IN-VITRO-TEST SYSTEMS)
Molecularbiology: In vitro-Transcription, -Translation; Cloning; PCR (MOLECULARBIOLOGY)
Signal transduction: Sodium- and Calcium-Imaging, intracellular pH (single cells und cell suspensions) [Video-Imaging], Radio-receptor assays (different receptors in the range of the GABA, glutamate, adrenalin, dopamine and serotonin related neurotransmission); MAO-A, -B assay; Synaptosomal neurotransmitter re-uptake [radio assay]; Neurotransmitter levels [HPLC]; Transduction systems (PLC, adenylatcyclase, a.o.) (IN-VITRO-TEST SYSTEMS)
Membrane biology: Subcellular fractions, membrane fluidity, membrane analysis (cholesterol, phospholipids [HPLC, TLC], acyl-chain spectrum [GC-MS], transbilayer-cholesterol-distribution, Lipid Rafts [WP], membrane modulation. (IN-VITRO-TEST SYSTEMS)
Characterisation of drugs in functional receptor models, structure activity models (IN-VITRO-TEST SYSTEMS)
Analytics: AAS-FI, HPLC-UV, HPLC-ECD, (DRUG-ANALYTICS)
Cell-Models: Blood Brain Barrier-models (PBCEC- und VLB-Cells), Alzheimer models (PC12swAPP-Cells, HEKswAPP-Cells) (IN-VITRO-TEST SYSTEMS)
Animal models: Transgenic Alzheimer models (PS1-, APP-mouse), aging model (mouse), cardiomyopathic-model (Hamster) (IN-VIVO-TEST SYSTEMS)

Publications

Keil U, Scherping I, Hauptmann S, Schuessel K, Eckert A, Muller WE. Piracetam improves mitochondrial dysfunction following oxidative stress. Br J Pharmacol (2006) 147: 199-208 (IN-VITRO-TEST SYSTEMS, IN-VIVO-TEST SYSTEMS)
Eckert GP, Wood WG, Muller WE. Membrane disordering effects of beta-amyloid peptides. Subcell Biochem (2005) 38: 319-337 (PATHOMOLECULAR MECHANISMS)
Schussel K, Schafer S, Bayer TA, Czech C, Pradier L, Muller-Spahn F, Muller WE, Eckert A. Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice. Neurobiol Dis (2005) 18: 89-99 (IN-VIVO-TEST SYSTEMS)
Weber CC, Kressmann S, Ott M, Fricker G, Muller WE. Inhibition of P-glycoprotein function by several antidepressants may not contribute to clinical efficiacy. Pharmacopsychiatry (2005) 38: 293-300 (IN-VITRO-TEST SYSTEMS)
Treiber K, Singer A, Henke B, Müller WE. Hyperforin activates nonselective cation channels (NSCCs).
Br J Pharmacol (2005) 145: 75-83 (IN-VITRO-TEST SYSTEMS)
Keil U, Bonert A, Marques CA, Scherping I, Weyermann J, Strosznajder JB, Muller-Spahn F, Haass C, Czech C, Pradier L, Müller WE, Eckert A. Amyloid beta-induced changes in nitric oxide production and mitochondrial activity lead to apoptosis. J Biol Chem (2004) 279: 50310-20 (IN-VITRO-TEST SYSTEMS)
Eckert GP, Wood WG, Müller WE. Statins: drugs for Alzheimer's disease? J Neural Transm. (2005) 112: 1057-71 (PATHOMOLECULAR MECHANISMS)
Schaffer S, Müller WE, Eckert GP. Tocotrienols: constitutional effects in aging and disease. J Nutr (2005) 135: 151-4 (PATHOMOLECULAR MECHANISMS)
Eckert GP, Keller JH, Jourdan C, Karas M, Volmer DA, Schubert-Zsilavecz M, Müller WE. Hyperforin modifies neuronal membrane properties in vivo. Neurosci Lett. (2004) 367: 139-43 (IN-VIVO-TEST SYSTEMS)
Schaffer S, Eckert GP, Müller WE, Llorach R, Rivera D, Grande S, Galli C, Visioli F. Hypochlorous acid scavenging properties of local Mediterranean plant foods. Lipids (2004) 39: 1239-47. (IN-VITRO-TEST SYSTEMS)
Schüssel K, Leutner S, Cairns NJ, Müller WE, Eckert A. Impact of gender on upregulation of antioxidant defence mechanisms in Alzheimer's disease brain. J Neural Transm (2004): 1167-82 (PATHOMOLECULAR MECHANISMS)
Eckert A, Keil U, Marques CA, Bonert A, Frey C, Schüssel K, Müller WE. Mitochondrial dysfunction, apoptotic cell death, and Alzheimer’s disease. Biochem Pharmacol (2003) 66:1627-1634 (IN-VIVO-TEST SYSTEMS and MOLECULARBIOLOGY)
Eckert GP, Igbavboa U, Müller WE, Wood G. Lipid rafts of purified mouse brain synaptosomes prepared with or without detergent reveal different lipid and protein domains. Brain Res (2003) 962:144-150 (IN-VITRO-TEST SYSTEMS, IN-VIVO-TEST SYSTEMS)
Fröstl B, Steiner B, Müller WE. Enhancement of proteolytic processing of the ß-amyloid precursor protein by Hyperforin. Biochem Pharmacol (2003) 66:2177-2184 (IN-VITRO-TEST SYSTEMS, MOLECULARBIOLOGY)
Kirsch C, Eckert GP, Müller WE. Statin effects on cholesterol micro-domains in brain plasma membranes. Biochem Pharmacol (2003) 65:843-856 (IN-VITRO-TEST SYSTEMS, PHARMACOLOGY)
Marques CA, Keil U, Bonert A, Steiner B, Haass C, Müller WE, Eckert A. Neurotoxic mechanisms caused by the Alzheimer’s disease-linked swedish amyloid precursur protein mutation. Oxidative stress, caspases, and the JNK pathway. J Biol Chem (2003) 278:28294-28302 (IN-(VITRO-TEST SYSTEMS, MOLECULARBIOLOGY)
Wood WG, Eckert GP, Igbavboa U, Müller WE. Amyloid beta-protein interactions with membranes and cholesterol: causes or casualties of Alzheimer’ disease. Biochim Biophys Acta (2003) 1610:281-290 (IN-VITRO-TEST SYSTEMS)

Staff:

Director:

Prof. Dr. rer. nat. Walter E. Müller

Work group leader:

Prof. Dr. W.E. Müller (Neuropsychopharmacology, agents against depression and anxiety: mode of action)
Dr. phil. nat. G. Eckert (Cerebral lipid-homeostasis, membrane biology, neuroprotection, new drug targets for dementia)
Dr. phil nat. Kristina Leuner (Neuropsychopharmacology, molecular mechanisms of antidepressants and sedatives)
Dr. phil nat. Uta Lipka (Pathomolecular mechanisms of Alzheimer’s disease)

ZAFES-Coordinators: