taking pain out of ngf a “painless” ngf mutant, linked to hereditary sensory autonomic neuropathy type v, with full neurotrophic activity疼痛,神经生长因子u201c无痛u201d神经生长因子突变体,与遗传性感觉自主神经病变类型v,与完整的神经营养活性.pdfVIP

Taking Pain Out of NGF: A ‘‘Painless’’ NGF Mutant, Linked to Hereditary Sensory Autonomic Neuropathy Type V, with Full Neurotrophic Activity 1,2 3 4 1 5 Simona Capsoni , Sonia Covaceuszach , Sara Marinelli , Marcello Ceci , Antonietta Bernardo , Luisa 5 3 4 1,2 Minghetti , Gabriele Ugolini , Flaminia Pavone , Antonino Cattaneo * 1 European Brain Research Institute, Rome, Italy, 2 Scuola Normale Superiore, Pisa, Italy, 3 Rottapharm Biotech s.r.l., Trieste, Italy, 4 Institute of Neuroscience, Consiglio ` Nazionale delle Ricerche, Rome, Italy, 5 Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Rome, Italy Abstract During adulthood, the neurotrophin Nerve Growth Factor (NGF) sensitizes nociceptors, thereby increasing the response to noxious stimuli. The relationship between NGF and pain is supported by genetic evidence: mutations in the NGF TrkA receptor in patients affected by an hereditary rare disease (Hereditary Sensory and Autonomic Neuropathy type IV, HSAN IV) determine a congenital form of severe pain insensitivity, with mental retardation, while a mutation in NGFB gene, leading to the aminoacid substitution R100W in mature NGF, determines a similar loss of pain perception, without overt cognitive neurological defects (HSAN V). The R100W mutation provokes a reduced processing of proNGF to mature NGF in cultured cells and a higher percentage of neurotrophin secreted is in the proNGF form. Moreover, using Surface Plasmon Resonance we s