Pharmakologisches Institut für Naturwissenschaftler -
Prof. Dr. Walter E. Müller

Expertise

Neurodegeneration und neuroprotektive Wirkstoffe
Oxidativer Stress und Antioxidantien
Antidepressive und anxiolytische Wirkmechanismen

Methoden und Geräte

Apoptose und Nekrose: DNA-Fragmentierung [FACS]; Nucleosomen-ELISA, TUNEL-Färbung [Fluoreszenzmikroskop]; MTT-, LDH-, ATP-Assay (IN-VITRO-TESTSYSTEME)
Immunologie: Markerbestimmung (CD-3, CD-4, CD-8, IL-2, IL-6 u.) [FACS], Expressionsbestimmung Bcl-2, Bax u.a. (IN-VITRO-TESTSYSTEME)
Oxidativer Stress: Enzymaktivitätsbestimmungen (SOD, GPx u.a.); GSH-Spiegel; MDA- und HNE-Bestimmung; Antioxidative Kapazität (TEAC), Hydroperoxid-Bestimmung, Hämoglobin-Degradations-Assay, Guaiacol-Oxidations-Assay (IN-VITRO-TESTSYSTEME)
Molekularbiologie: In vitro-Transkription, -Translation; Klonierungen; PCR (MOLEKULARBIOLOGIE)
Signaltransduktion: Natrium- und Calcium-Imaging, intrazelluläre pH-Wertmessung (an Einzelzellen und Zellsuspensionen) [Video-Imaging], Radiorezeptorassays (verschiedene Rezeptoren im Bereich der GABAergen, glutaminergen, noradrenergen, dopaminergen und serotonergen Neurotransmission); MAO-A, -B Assay; Synaptosomale Neurotransmitteraufnahme [Radioassay]; Neurotransmitterbestimmung [HPLC]; Transduktionssysteme (PLC, Adenylatcyclase, u.a.) (IN-VITRO-TESTSYSTEME)
Membranbiochemie: Subzelluläre Fraktionierung, Fluiditätsuntersuchungen, Membrananalyse (Cholesterin, Phospholipide [HPLC, TLC], Fettsäurespektrum [GC-MS], Transbilayer-Cholesterin-Distribution, Isolierung und Charakterisierung von Lipid Rafts [WP], Membranmodulation.
Charakterisierung von Wirkstoffen in funktionellen Rezeptormodellen, Struktur-Wirkungsbeziehungen(IN-VITRO-TESTSYSTEME)
Analytik: AAS-FI, HPLC-UV, HPLC-ECD, (WIRKSTOFF-ANALYTIK)
Zell-Modelle: Bluthirnschranken-Modell (PBCEC- und VLB-Zellen), Alzheimer Modell (PC12swAPP-Zellen, HEKswAPP-Zellen)
Tierexperimentelle Methoden: (IN-VIVO-TESTSYSTEME)
- Transgene Alzheimer Modelle (PS1, APP), Maus-Alterungsmodell, Kardiomyopathie-Modell (Hamster),

Publikationen

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)

Mitarbeiter:

Direktor:

Prof. Dr. rer. nat. Walter E. Müller

Arbeitsgruppenleiter:

Prof. Dr. W.E. Müller (Neuropsychopharmakologie, Wirkmechanismen von Antidepressiva und Anxiolytika)
Dr. phil. nat. G. Eckert (Cerebrale Lipid Homeostase, Membranbiologie, Neuroprotektion, neue Targets für Antidementiva, zerebrale Lipidhomöostase)
Dr. phil. nat. Kristina Leuner (Molekulare Wirkmechanismen von Antidepressiva and Sedativa)
Dr. phil nat. Uta Lipka (Pathomechanismen der Alzheimer Demenz)

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