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8. hNGF Peptides Elicit the NGF-TrkA Signalling Pathway in Cholinergic Neurons and Retain Full Neurotrophic Activity in the DRG Assay

Author

Triaca, Viviana, primary, Fico, Elena, additional, Sposato, Valentina, additional, Caioli, Silvia, additional, Ciotti, Maria Teresa, additional, Zona, Cristina, additional, Mercanti, Delio, additional, La Mendola, Diego, additional, Satriano, Cristina, additional, Rizzarelli, Enrico, additional, Tirassa, Paola, additional, and Calissano, Pietro, additional

Published
2020
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9. Mining clinical and laboratory data of neurodegenerative diseases by Machine Learning: transcriptomic biomarkers

Author

Arisi, Ivan, primary, Mecocci, Patrizia, additional, Bruno, Giuseppe, additional, Canevelli, Marco, additional, Tsolaki, Magda, additional, Pelteki, Natalia, additional, Stocchi, Fabrizio, additional, Vacca, Laura, additional, Fiscon, Giulia, additional, Bertolazzi, Paola, additional, D'Onofrio, Mara, additional, Brandi, Rossella, additional, Sonnessa, Michele, additional, Campanelli, Alessandra, additional, Florio, Rita, additional, Sposato, Valentina, additional, Malerba, Francesca, additional, and Cattaneo, Antonino, additional

Published
2018
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10. The Medial Septum Is Insulin Resistant in the AD Presymptomatic Phase: Rescue by Nerve Growth Factor-Driven IRS1 Activation

Author

Sposato, Valentina, primary, Canu, Nadia, additional, Fico, Elena, additional, Fusco, Salvatore, additional, Bolasco, Giulia, additional, Ciotti, Maria Teresa, additional, Spinelli, Matteo, additional, Mercanti, Delio, additional, Grassi, Claudio, additional, Triaca, Viviana, additional, and Calissano, Pietro, additional

Published
2018
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13. Association of TrkA and APP Is Promoted by NGF and Reduced by Cell Death-Promoting Agents

Author

Canu, Nadia, primary, Pagano, Ilaria, additional, La Rosa, Luca Rosario, additional, Pellegrino, Marsha, additional, Ciotti, Maria Teresa, additional, Mercanti, Delio, additional, Moretti, Fabiola, additional, Sposato, Valentina, additional, Triaca, Viviana, additional, Petrella, Carla, additional, Maruyama, Ichiro N., additional, Levi, Andrea, additional, and Calissano, Pietro, additional

Published
2017
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14. NGF controls APP cleavage by downregulating APP phosphorylation at Thr668: relevance for Alzheimer's disease

Author

Triaca, Viviana, primary, Sposato, Valentina, additional, Bolasco, Giulia, additional, Ciotti, Maria Teresa, additional, Pelicci, Piergiuseppe, additional, Bruni, Amalia C., additional, Cupidi, Chiara, additional, Maletta, Raffaele, additional, Feligioni, Marco, additional, Nisticò, Robert, additional, Canu, Nadia, additional, and Calissano, Pietro, additional

Published
2016
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15. The Medial Septum Is Insulin Resistant in the AD Presymptomatic Phase: Rescue by Nerve Growth Factor-Driven IRS1 Activation.

Author

Sposato, Valentina, Canu, Nadia, Fico, Elena, Fusco, Salvatore, Bolasco, Giulia, Ciotti, Maria Teresa, Spinelli, Matteo, Mercanti, Delio, Grassi, Claudio, Triaca, Viviana, and Calissano, Pietro

Abstract

Basal forebrain cholinergic neurons (BFCN) are key modulators of learning and memory and are high energy-demanding neurons. Impaired neuronal metabolism and reduced insulin signaling, known as insulin resistance, has been reported in the early phase of Alzheimer's disease (AD), which has been suggested to be "Type 3 Diabetes." We hypothesized that BFCN may develop insulin resistance and their consequent failure represents one of the earliest event in AD. We found that a condition reminiscent of insulin resistance occurs in the medial septum of 3 months old 3×Tg-AD mice, reported to develop typical AD histopathology and cognitive deficits in adulthood. Further, we obtained insulin resistant BFCN by culturing them with high insulin concentrations. By means of these paradigms, we observed that nerve growth factor (NGF) reduces insulin resistance in vitro and in vivo. NGF activates the insulin receptor substrate 1 (IRS1) and rescues c-Fos expression and glucose metabolism. This effect involves binding of activated IRS1 to the NGF receptor TrkA, and is lost in presence of the specific IRS inhibitor NT157. Overall, our findings indicate that, in a well-established animal model of AD, the medial septum develops insulin resistance several months before it is detectable in the neocortex and hippocampus. Remarkably, NGF counteracts molecular alterations downstream of insulin-resistant receptor and its nasal administration restores insulin signaling in 3×Tg-AD mice by TrkA/IRS1 activation. The cross-talk between NGF and insulin pathways downstream the insulin receptor suggests novel potential therapeutic targets to slow cognitive decline in AD and diabetes-related brain insulin resistance. [ABSTRACT FROM AUTHOR]

Published
2019
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