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Laboratory of Pharmacodynamics and Pharmacokinetics

Research Activities

The main research area focuses on amyloidogenic proteins and on the identification of new therapeutic strategies for the corresponding diseases, with a range of approaches including in silico methods, in vitro biochemical assays and analysis of molecular interactions (in particular by Surface Plasmon Resonance), up to in vivo pharmacokinetics (PK) with HPLC-MS. These approaches are also applied for the: characterization of nanoparticles (eg their interaction with biological targets and PK properties); identification and PK profile of anti-ischemic lectine inhibitors; PK properties of new psychoactive substances; analysis of endogenous molecules used as biomarkers.

 


Main Research Projects:

• Misfolding protein diseases: i) characterization of the anti-amyloidogenic effects of molecular chaperones and development of synthetic derivatives with similar properties; ii) identification of biological effectors underlying amyloid-β toxicity, using a new mutagenesis approach in C. elegans; iii) identification and characterization of conformational antibodies suitable for the specific recognition of toxic oligomeric aggregates, potentially useful for diagnosis/therapy of amyloidosis; iv) analysis of the PK profile of doxycycline in animal models of Alzheimer’s disease and prion disease.

• Development of innovative assays based on Surface Plasmon Resonance for the determination of plasmatic and tissue concentrations of nanoparticles and therapeutic antibodies; and for the screening of ligands/inhibitors of Mannose Binding Lectin, with potential anti-ischemic activity.

• Development of new analytical methods to measure plasma and tissue levels of New Psychoactive Substances; PK studies carried out in parallel with the evaluation of the pharmaco-toxicological effects of these substances.

• Analysis of the brain levels of metabolites of the kinurenine pathway after cardiac arrest: correlation with plasmatic levels and role in neurological consequences.

Selected publications

  • Code: 17367
    Beeg M, Nobili A, Orsini B, Rogai F, Gilardi D, Fiorino G, Danese S, Salmona M, Garattini S, Gobbi M
    A surface plasmon resonance-based assay to measure serum concentrations of therapeutic antibodies and anti-drug antibodies
    Sci Rep 2019; 9: 2064
    IF: 4.122
    Status: Published
    PubMed icon
  • Code: 17525
    Lucchetti J, Fracasso C, Balducci C, Passoni A, Forloni G, Salmona M, Gobbi M
    Plasma and brain concentrations of doxycycline after single and repeated doses in wild-type and APP23 mice
    J Pharmacol Exp Ther 2019; 368: 32-40
    IF: 3.706
    Status: Published
    PubMed icon
  • Code: 15701
    Beeg M, Stravalaci M, Romeo M, Carra A D, Cagnotto A, Rossi A, Diomede L, Salmona M, Gobbi M
    Clusterin binds to Aβ1-42 oligomers with high affinity and interferes with peptide aggregation by inhibiting primary and secondary nucleation
    J Biol Chem 2016; 291: 6958-6966
    IF: 4.125
    Status: Published
    Alternative link icon
  • Code: 15802
    Stravalaci M, Tapella L, Beeg M, Rossi A, Joshi P, Pizzi E, Mazzanti M, Balducci C, Forloni G, Biasini E, Salmona M, Diomede L, Chiesa R, Gobbi M
    The anti-prion antibody 15B3 detects toxic amyloid-β oligomers
    J Alzheimers Dis 2016; 53: 1485-1497
    IF: 3.731
    Status: Published
    PubMed icon
  • Code: 14154
    Fracasso C, Bagnati R, Passoni A, Guiso G, Cantoni L, Riva A, Morazzoni P, Gobbi M
    Brain uptake of tetrahydrohyperforin and potential metabolites after repeated dosing in mice
    J Nat Prod 2015; 78: 2029-2035
    IF: 3.662
    Status: Published
    PubMed icon
  • Code: 14528
    Beeg M, Diomede L, Stravalaci M, Salmona M, Gobbi M
    Novel approaches for studying amyloidogenic peptides/proteins
    Curr Opin Pharmacol 2013; 13: 797-801
    IF: 4.227
    Status: Published
    PubMed icon
  • Code: 13975
    Stravalaci M, Bastone A, Beeg M, Cagnotto A, Colombo L, Di Fede G, Tagliavini F, Cantu' L, Del Favero E, Mazzanti M, Chiesa R, Salmona M, Diomede L, Gobbi M
    Specific recognition of biologically active amyloid-β oligomers by a new surface plasmon resonance-based immunoassay and an in vivo assay in Caenorhabditis elegans
    J Biol Chem 2012; 287: 27796-27805
    IF: 4.651
    Status: Published
    PubMed icon
  • Code: 13811
    Orsini F, Villa P, Parrella S, Zangari R, Zanier E R, Gesuete R, Stravalaci M, Fumagalli S, Ottria R, Reina J J, Paladini A, Micotti E, Ribeiro-Viana R, Rojo J, Pavlov V I, Stahl G L, Bernardi A, Gobbi M, De Simoni M G
    Targeting mannose-binding lectin confers long-lasting protection with a surprisingly wide therapeutic window in cerebral ischemia
    Circulation 2012; 126: 1484-1494
    IF: 15.202
    Status: Published
    PubMed icon
  • Code: 15175
    Ristagno G, Latini R, Vaahersalo J, Masson S, Kurola J, Varpula T, Lucchetti J, Fracasso C, Guiso G, Montanelli M, Barlera S, Gobbi M, Tiainen M, Pettilä V, Skrifvars M B, FINNRESUSCI Investigators
    Early activation of the kynurenine pathway predicts early death and long-term outcome in patients resuscitated from out-of-hospital cardiac arrest
    J Am Heart Assoc 2014; 3: e001094
    IF: 4.306
    Status: Published
    PubMed icon