Director

  foto_cattaneo  
Prof. Antonino Cattaneo
Full Professor of Neurobiology
 
 
antonino.cattaneo@sns.it
 

After obtaining a Degree in Physics at the University of Rome La Sapienza (1976), Antonino Cattaneo undertook research in Neurobiology at Scuola Normale Superiore with Lamberto Maffei, working on the encoding of visual information by cells of the the visual cortex (1977-1980). He then worked at the CNR Institute of Cell Biology with Rita Levi Montalcini and Pietro Calissano on the molecular mechanisms of neuronal differentiation by Nerve Growth Factor (1981-1984) and at the MRC Laboratory of Molecular Biology (Cambridge UK) (1985-1989) with Cesar Milstein and Michael Neuberger, where he demonstrated the experimental strategy of ectopical antibody expression targeted to different subcellular compartments, for protein interference in the nervous system and other biological systems.

From 1991 he was Full Professor of Biophysics at the International School for Advanced Studies (SISSA)  in Trieste, where as Head of the Biophysics Sector and Deputy Director he was involved in setting up from scratch SISSA Neuroscience Program. From 2004 he assisted Rita Levi-Montalcini in launching the European Brain Research Institute, for which he served as the Scientific Director, before joining Scuola Normale Superiore in 2009.

He is a member of the European Molecular Biology Organization (EMBO) and of the Accademia delle Scienze dei XL, has been a Visiting Fellow at Trinity College (University of Cambridge, UK) and has received many international awards for his research. He is the author of over 180 peer reviewed pubblications in international scientific journals and an inventor on several biotechnology patents, based on his  research, all of which have been industrially exploited.

His research led to i) the development of the intrabody protein silencing technology, ii) the discovery of proNGF/NGF imbalance as an unpstream driver mechanism for Alzheimer’s neurodegeneration, iii) the development of innovative neurotrophic factor based therapies for neurodegenerative diseases. Two humanized recombinant antibodies developed in his laboratory are currently under clinical testing in man. His current research aims at deciphering the molecular and cellular mechanisms that lead to neurodegeneration, at studying protein misfolding in living cells and at identifying new targets for the development of new therapies for neurodegenerative diseases (most notably Alzheimer’s disease), based on these mechanisms. A strong interest in his research is dedicated to the development of new technologies and experimental strategies for intefering with protein function in living neurons in a spatially and temporally precise fashion (intrabodies).

Selected Publications

  1. Cattaneo A, Rapposelli B, Calissano P (1988) Three distinct types of monoclonal antibodies after long-term immunization of rats with mouse nerve growth factor. J Neurochem 50:1003-1010.
  2. Biocca S, Neuberger MS, Cattaneo A (1990) Expression and targeting of intracellular antibodies in mammalian cells. Embo J 9:101-108.
  3. Piccioli P, Ruberti F, Biocca S, Di Luzio A, Werge TM, Bradbury A, Cattaneo A (1991) Neuroantibodies: molecular cloning of a monoclonal antibody against substance P for expression in the central nervous system. Proc Natl Acad Sci U S A 88:5611-5615.
  4. Bradbury A, Persic L, Werge T, Cattaneo A (1993) Use of living columns to select specific phage antibodies. Nature Biotechnology (N Y) 11:1565-1569.
  5. Tavladoraki P, Benvenuto E, Trinca S, De Martinis D, Cattaneo A, Galeffi P (1993) Transgenic plants expressing a functional single-chain Fv antibody are specifically protected from virus attack. Nature 366:469-472.
  6. Berardi N, Cellerino A, Domenici L, Fagiolini M, Pizzorusso T, Cattaneo A, Maffei L (1994) Monoclonal antibodies to nerve growth factor affect the postnatal development of the visual system. Proc Natl Acad Sci U S A 91:684-688.
  7. Biocca S, Pierandrei-Amaldi P, Campioni N and Cattaneo A (1994) Intracellular immunization with cytosolic recombinant antibodies. Nature Biotechnology (N Y) 12:396-399.
  8. Biocca S, Cattaneo A (1995) Intracellular immunization: antibody targeting to subcellular compartments. Trends Cell Biol 5:248-252.
  9. Biocca S, Ruberti F, Tafani M, Pierandrei-Amaldi P and Cattaneo A (1995) Redox state of single chain Fv fragments targeted to the endoplasmic reticulum, cytosol and mitochondria. Nature Biotechnology (N Y) 13:1110-1115.
  10. Bradbury A, Cattaneo A (1995) The use of phage display in neurobiology. Trends Neurosci 18:243-249.
  11. Piccioli P, Di Luzio A, Amann R, Schuligoi R, Surani MA, Donnerer J, Cattaneo A (1995) Neuroantibodies: ectopic expression of a recombinant anti-substance P antibody in the central nervous system of transgenic mice. Neuron 15:373-384.
  12. Tongiorgi E, Righi M, Cattaneo A (1997) Activity-dependent dendritic targeting of BDNF and TrkB mRNAs in hippocampal neurons. J Neurosci 17:9492-9505.
  13. Cattaneo A, Biocca S (1999) The selection of intracellular antibodies. Trends Biotechnol 17:115-121.
  14. Cattaneo A, Capsoni S, Margotti E, Righi M, Kontsekova E, Pavlik P, Filipcik P, Novak M (1999) Functional blockade of tyrosine kinase A in the rat basal forebrain by a novel antagonistic anti-receptor monoclonal antibody. J Neurosci 19:9687-9697.
  15. Visintin M, Tse E, Axelson H, Rabbitts TH, Cattaneo A (1999) Selection of antibodies for intracellular function using a two-hybrid in vivo system. Proc Natl Acad Sci U S A 96:11723-11728.
  16. Capsoni S, Ugolini G, Comparini A, Ruberti F, Berardi N, Cattaneo A (2000b) Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice. Proc Natl Acad Sci U S A 97:6826-6831.
  17. Fasulo L, Ugolini G, Visintin M, Bradbury A, Brancolini C, Verzillo V, Novak M, Cattaneo A (2000) The neuronal microtubule-associated protein tau is a substrate for caspase-3 and an effector of apoptosis. J Neurochem 75:624-633.
  18. Pesavento E, Margotti E, Righi M, Cattaneo A, Domenici L (2000) Blocking the NGF-TrkA interaction rescues the developmental loss of LTP in the rat visual cortex: role of the cholinergic system. Neuron 25:165-175.
  19. Righi M, Tongiorgi E, Cattaneo A (2000) Brain-derived neurotrophic factor (BDNF) induces dendritic targeting of BDNF and tyrosine kinase B mRNAs in hippocampal neurons through a phosphatidylinositol-3 kinase-dependent pathway. J Neurosci 20:3165-3174.
  20. Ruberti F, Capsoni S, Comparini A, Di Daniel E, Franzot J, Gonfloni S, Rossi G, Berardi N, Cattaneo A (2000) Phenotypic knockout of nerve growth factor in adult transgenic mice reveals severe deficits in basal forebrain cholinergic neurons, cell death in the spleen, and skeletal muscle dystrophy. J Neurosci 20:2589-2601.
  21. Capsoni S, Giannotta S, Cattaneo A (2002a) Beta-amyloid plaques in a model for sporadic Alzheimer’s disease based on transgenic anti-nerve growth factor antibodies. Mol Cell Neurosci 21:15-28.
  22. Capsoni S, Giannotta S, Cattaneo A (2002b) Nerve growth factor and galantamine ameliorate early signs of neurodegeneration in anti-nerve growth factor mice. Proc Natl Acad Sci U S A 99:12432-12437.
  23. Visintin M, Settanni G, Maritan A, Graziosi S, Marks JD, Cattaneo A (2002) The intracellular antibody capture technology (IACT): towards a consensus sequence for intracellular antibodies. J Mol Biol 317:73-83.
  24. Visintin M, Meli GA, Cannistraci I, Cattaneo A (2004a) Intracellular antibodies for proteomics. J Immunol Methods 290:135-153.
  25. De Rosa R, Garcia AA, Braschi C, Capsoni S, Maffei L, Berardi N, Cattaneo A (2005) Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice. Proc Natl Acad Sci U S A 102:3811-3816.
  26. Fasulo L, Ugolini G, Cattaneo A (2005) Apoptotic effect of caspase-3 cleaved tau in hippocampal neurons and its potentiation by tau FTDP-mutation N279K. J Alzheimers Dis 7:3-13.
  27. Ugolini G, Marinelli S, Covaceuszach S, Cattaneo A, Pavone F (2007) The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain. Proc.Natl Acad Sci USA 104:2985-2990.
  28. Melchionna T and Cattaneo A (2007) A protein silencing switch by ligand-induced proteasome targeting intrabodies. J Mol Biol 374:641-54.
  29. Covaceuszach S, Cassetta A., Konarev PV, Gonfloni S, Rudolph R, Svergun D, Lamba D, and Cattaneo A (2008) Dissecting NGF interactions with TrkA and p75 receptors by structural and functional studies of an anti-NGF neutralizing antibody. J. Mol. Biol., 381: 881-896.
  30. Visintin M, Melchionna T, Cannistraci I and Cattaneo A  (2008) In vivo selection of intrabodies specifically targeting protein-protein interactions: a general platform for an “undruggable” class of disease targets. J. Biotechnol., 135: 1-15.
  31. Cattaneo A, Capsoni S and Paoletti F (2008) Towards non invasive Nerve Growth Factor therapies for Alzheimer’s Disease. Journal of Alzheimer’s Disease 15, 255-283.
  32. Meli G, Visintin M, Cannistraci I, Cattaneo A (2009) Direct in vivo intracellular selection of conformation-sensitive antibody domains targeting Alzheimer’s amyloid-beta oligomers. J Mol Biol. 2009 Apr 3;387(3):584-606.
  33. Lagostena L, Rosato-Siri M, D’Onofrio M, Brandi R, Arisi I, Capsoni S, Franzot J, Cattaneo A and Cherubini  E (2010) In the adult hippocampus, chronic NGF deprivation shifts GABAergic signaling from the hyperpolarizing to the depolarizing direction. J. Neuroscience 30:85.
  34. Covaceuszach S,  Capsoni S, , Marinelli S, Pavone F , Ceci M, Ugolini G, Vignone D,  Amato G, Paoletti F, Lamba D and Cattaneo A (2010) In vitro binding properties of a “painless” NGF mutein, linked to Hereditary Sensory Autonomic neuropathy Type V. Biophys. Biochem Res. Comm. (391, 824-829).
  35. Capsoni, S., Tiveron, C., Amato, G., Vignone, D., Cattaneo, A. (2010) Dissecting the involvement of Tropomyosin kinase A and p75 neurotrophin receptor signaling in NGF deficit-induced neurodegeneration. Proc Natl Acad Sci USA  107: 12299-12304.
  36. Houeland G, Romani A, Marchetti C, Amato G, Capsoni S, Cattaneo A, Marie H (2010) Transgenic mice with chronic NGF deprivation and Alzheimer’s disease-like pathology display hippocampal region-specific impairments in short- and long-term plasticities. J Neurosci. 30:13089-94.
  37. Capsoni S, Covaceuszach S, Marinelli S, Ceci M, Bernardo A, Minghetti L, Ugolini G, Pavone F, Cattaneo A (2011) Taking pain out of NGF: a “painless” NGF mutant, linked to hereditary sensory autonomic neuropathy type V, with full neurotrophic activity. PLoS One 6(2):e17321
  38. Paoletti F, Malerba F, Kelly G, Noinville S, Lamba D, Cattaneo A and Pastore A  (2011) Conformational Plasticity of proNGF. PLoS One 6(7): e22615.
  39. Covaceuszach S, Marinelli S, Krastanova I, Ugolini G, Pavone F, Lamba D, Cattaneo A (2012) Single Cycle Structure-based Humanization of an Anti-Nerve Growth Factor Therapeutic Antibody. PLoS One 7: e32212.
  40. Capsoni S, Marinelli S, Ceci M, Vignone D, Amato G, Malerba F, Paoletti F, Meli G, Viegi A, Pavone F, Cattaneo A (2012)Intranasal “painless” Human Nerve Growth Factors Slows Amyloid Neurodegeneration and Prevents Memory Deficits in App X PS1 Mice. PLoS One 7: e37555.
  41. Tiveron C et al (2013) proNGF/NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice. Cell Death and Differ., 20(8):1017-30. doi: 10.1038/cdd.2013.22. Epub 2013 Mar 29.
  42. Meli G, Lecci A, Manca A, Krako N, Albertini V, Benussi L, Ghidoni R and Cattaneo A (2014) Conformational targeting of intracellular Amyloid-beta oligomers demonstrates their pathological oligomerization inside the endoplasmic reticulum. Nature Communications (in press).