The European Brain Research Institute Rome
Via del Fosso di Fiorano 64


00143 - Rome
Italy

+39-06-50170-3118
+39-06-50170-3315
a.cattaneo@ebri.it

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The research of Antonino Cattaneo has been inspired by the classical and seminal experiments of Rita Levi Montalcini on immunosympathectomy, whereby she exploited the use of anti NGF antibodies to formally demonstrate the role of Nerve Growth Factor (NGF) in vivo.
In fact, the scientific career and research achievements of Antonino Cattaneo have followed a parallel track, combining a deep interest and knowledge in molecular neurobiology (with particular regard to the roles of Nerve Growth Factor (NGF) and neurotrophins in the Central Nervous System (CNS)), together with the development of technologies exploiting recombinant antibodies for protein knock-out (neuroantibodies and intrabodies), with a particular focus on CNS applications. In this field, Cattaneo has pioneered and developed the neuroantibody strategy, whereby the expression of recombinant antibodies in the CNS is used to interfere with neuronal functions, creating experimental models  for mechanistic studies. In further developments, Cattaneo has developed the targeting and use of intracellular antibodies (intrabodies) to achieve protein knock-out in different subcellular compartments. The intracellular antibody technology, which exploits the targeting of antibodies to subcellular compartments, has  been developed towards its application to functional genomics and proteomics.
This unique and original combination of recombinant antibody technologies and molecular neurobiology has allowed to develop transgenic models, based on the expression of recombinant antibodies to NGF in the brain of adult transgenic mice. The use of this novel experimental strategy has allowed to demonstrate that interfering specifically with the function of NGF in the adult Central Nervous System leads to a progressive neurodegenerative phenotype that recapitulates in a comprehensive way most of the major hallmarks of Alzheimer’s Disease (AD), including amyloid plaques, cholinergic deficits, neuronal loss, neurofibrillary tangles and tau abnormalities, as well as synaptic and behavioural deficits. This work allowed to extend our understanding of the role of NGF in the CNS and allowed, in particular, to link the (abnormal) signalling of NGF and of its precursor form proNGF to phenotypic endpoints relevant for Alzheimer’s disease (AD) and to study the mechanism of AD-like neurodegeneration in the rodent brain. This led to his current hypothesis of “too little NGF-too much proNGF” as a new framework for the study of Alzheimer’s disease pathological mechanisms.
This work has significant therapeutical implications, linked to developing therapeutical strategies for AD based on modulating the activity of the NGF/proNGF signalling pathway in the brain, and has significantly contributed to validate the now well accepted concept of NGF as a therapeutical gene/protein for the treatment of Alzheimer’s Disease. Since, in a therapeutical perspective, NGF needs to be locally delivered to the CNS, in order to avoid conflicting undesired effects  by NGF on  peripheral targets, Cattaneo has exploited and developed an intranasal delivery route for the access of NGF to the brain, obtaining conclusive proof of principle evidence for the ability of olfactory delivered NGF to rescue neurodegeneration in animal models. Olfactory delivered NGF is now a viable therapeutical option for AD, that is being developed towards clinical applications.