title: A comparative analysis of the structural, functional and biological differences between Mouse and Human Nerve Growth Factor.
abstract: NGF is the prototype member of the neurotrophin family of proteins that promote the survival and growth of selected neurons in the central and peripheral nervous systems. As for all neurotrophins, NGF is translated as a pre-pro-protein. Over the years, NGF and proNGF of either human or mouse origin, given their high degree of homology, have been exploited for numerous applications in biomedical sciences. The mouse NGF has been considered the golden-standard for bioactivity. Indeed, due to evolutionary relatedness to human NGF and to its ready availability and by assuming identical properties to its human counterpart, the mouse NGF, isolated and purified from sub-maxillary glands, has been tested not only in laboratory practice and in preclinical models, but it has also been evaluated in several human clinical trials. Aiming to validate this assumption, widely believed, we performed a comparative study of the biochemical and biophysical properties of the mouse and human counterparts of NGF and proNGF. The mature and the precursor proteins of either species strikingly differ in their biophysical profiles and, when tested for ligand binding to their receptors, in their in vitro biological activities. We provide a structural rationale that accounts for their different functional behaviors. Despite being highly conserved during evolution, NGF and proNGF of mouse and human origins show distinct properties and therefore special care must be taken in performing experiments with cross-species systems in the laboratory practice, in developing immunoassays, in clinical trials and in pharmacological treatments.
authors.affiliation: Neurotrophic Factors and Neurodegenerative Diseases Unit, European Brain Research Institute, "Rita Levi-Montalcini" Foundation, Via del Fosso di Fiorano 64, Rome 00143, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Paoletti
authors.affiliation: Neurotrophic Factors and Neurodegenerative Diseases Unit, European Brain Research Institute, "Rita Levi-Montalcini" Foundation, Via del Fosso di Fiorano 64, Rome 00143, Italy; Neurobiology Laboratory of Biology, Scuola Normale Superiore, Piazza dei Cavalieri 7, Pisa 56126, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Malerba
authors.affiliation: Neurotrophic Factors and Neurodegenerative Diseases Unit, European Brain Research Institute, "Rita Levi-Montalcini" Foundation, Via del Fosso di Fiorano 64, Rome 00143, Italy.
authors.forename: Bruno Bruni
authors.initials: BB
authors.lastname: Ercole
authors.affiliation: Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Area Science Park-Basovizza, S.S. 14 Km 163.5, Trieste I-34149, Italy.
authors.forename: Doriano
authors.initials: D
authors.lastname: Lamba
authors.affiliation: Neurotrophic Factors and Neurodegenerative Diseases Unit, European Brain Research Institute, "Rita Levi-Montalcini" Foundation, Via del Fosso di Fiorano 64, Rome 00143, Italy; Neurobiology Laboratory of Biology, Scuola Normale Superiore, Piazza dei Cavalieri 7, Pisa 56126, Italy. Electronic address: antonino.cattaneo@sns.it.
authors.forename: Antonino
authors.initials: A
authors.lastname: Cattaneo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D017124:Conserved Sequence; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology* / Q000648:ultrastructure; D011487:Protein Conformation; D011489:Protein Denaturation; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D020932:Nerve Growth Factor
keywords: Anti-NGF antibodies; Chemical/thermal denaturation; Mouse and human species; NGF; ProNGF; TF-1 cell proliferation assay