Neurotrophic Factors and Neurodegenerative Diseases


NGF structure (sml)
Molecular structure of the Nerve Growth Factor (NGF)

Mouse brain section (Cattaneo) (big)
Sections of a brain from a mouse, used as an experimental model for Alzheimer’s disease. This mouse has been genetically modified in order to generate typical features of neurodegenration shown here as brownish aggregates. This model represents a powerful tool for the study of the pathophysiology of Alzheimer’s disease.


The activity of neurotrophic factors on their target neurons in the adult and ageing CNS, as well as their selective availability and transport, represent a cross-road in the mechanisms that lead to neurodegeneration. The major interest in our laboratory is to study how abnormalities in the signalling and post-translational processing by neurotrophins in the CNS are linked to the progressive onset of neurodegeneration, and how this understanding may lead to develop new potential therapies for human neurodegenerative pathologies.

The research of Cattaneo’s lab 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 research activities of Cattaneo’s group follow a parallel track, combining an interest in molecular neurobiology of neurodegeneration (with particular regard to the roles of Nerve Growth Factor (NGF) and neurotrophins in the CNS), together with the development of technologies exploiting recombinant antibodies for protein knock-out in the CNS (neuroantibodies and intrabodies). In this field, we have 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, we have developed the targeting of intracellular antibodies (intrabodies) to achieve protein knock-out in different subcellular compartments.

This has allowed to demonstrate that interfering with the function of NGF in the adult CNS leads to a progressive neurodegenerative phenotype that recapitulates in a comprehensive way most of the major hallmarks of Alzheimer’s Disease (AD). Our current research activities are focussed on studying the mechanistic role of NGF in Alzheimer’s-like neurodegeneration, linking the (abnormal) signalling of NGF and of its precursor form proNGF to phenotypic endpoints relevant for Alzheimer’s disease (AD). We are guided in this work by our current hypothesis of “too little NGF-too much proNGF” as a new framework for the study of Alzheimer’s disease pathological mechanisms.



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