A Versatile Strategy for Signal Amplification Based on Core/Shell Silica Nanoparticles

Rampazzo, Enrico; Bonacchi, Sara; Genovese, Damiano; Juris, Riccardo; Sgarzi, Massimo; Montalti, Marco; Prodi, Luca; Zaccheroni, Nelsi; Tomaselli, Gaetano A.; Gentile, Salvatore; Satriano, Cristina; Rizzarelli, Enrico

doi:10.1002/chem.201101851

Cited by 43 publications

(46 citation statements)

References 30 publications

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“…To evaluate the effect of NGF(1–14) and Ac-NGF(1–14) on the intracellular copper trafficking, confocal microscopy imaging was used to scrutinize the cells stained with the intracellular probe of monovalent copper CS1 (Rampazzo et al, 2011). …”

Section: Resultsmentioning

confidence: 99%

The Inorganic Side of NGF: Copper(II) and Zinc(II) Affect the NGF Mimicking Signaling of the N-Terminus Peptides Encompassing the Recognition Domain of TrkA Receptor

Pandini

Satriano

Pietropaolo³

et al. 2016

Front. Neurosci.

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The nerve growth factor (NGF) N-terminus peptide, NGF(1–14), and its acetylated form, Ac-NGF(1–14), were investigated to scrutinize the ability of this neurotrophin domain to mimic the whole protein. Theoretical calculations demonstrated that non-covalent forces assist the molecular recognition of TrkA receptor by both peptides. Combined parallel tempering/docking simulations discriminated the effect of the N-terminal acetylation on the recognition of NGF(1–14) by the domain 5 of TrkA (TrkA-D5). Experimental findings demonstrated that both NGF(1–14) and Ac-NGF(1–14) activate TrkA signaling pathways essential for neuronal survival. The NGF-induced TrkA internalization was slightly inhibited in the presence of Cu2+ and Zn2+ ions, whereas the metal ions elicited the NGF(1–14)-induced internalization of TrkA and no significant differences were found in the weak Ac-NGF(1–14)-induced receptor internalization. The crucial role of the metals was confirmed by experiments with the metal-chelator bathocuproine disulfonic acid, which showed different inhibitory effects in the signaling cascade, due to different metal affinity of NGF, NGF(1–14) and Ac-NGF(1–14). The NGF signaling cascade, activated by the two peptides, induced CREB phosphorylation, but the copper addition further stimulated the Akt, ERK and CREB phosphorylation in the presence of NGF and NGF(1–14) only. A dynamic and quick influx of both peptides into PC12 cells was tracked by live cell imaging with confocal microscopy. A significant role of copper ions was found in the modulation of peptide sub-cellular localization, especially at the nuclear level. Furthermore, a strong copper ionophoric ability of NGF(1–14) was measured. The Ac-NGF(1–14) peptide, which binds copper ions with a lower stability constant than NGF(1–14), exhibited a lower nuclear localization with respect to the total cellular uptake. These findings were correlated to the metal-induced increase of CREB and BDNF expression caused by NGF(1–14) stimulation. In summary, we here validated NGF(1–14) and Ac-NGF(1–14) as first examples of monomer and linear peptides able to activate the NGF-TrkA signaling cascade. Metal ions modulated the activity of both NGF protein and the NGF-mimicking peptides. Such findings demonstrated that NGF(1–14) sequence can reproduce the signal transduction of whole protein, therefore representing a very promising drug candidate for further pre-clinical studies.

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Section: Resultsmentioning

confidence: 99%

The Inorganic Side of NGF: Copper(II) and Zinc(II) Affect the NGF Mimicking Signaling of the N-Terminus Peptides Encompassing the Recognition Domain of TrkA Receptor

Pandini

Satriano

Pietropaolo³

et al. 2016

Front. Neurosci.

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“…The probe has a K d of 3.6 pM for Cu + and may be used to detect Cu + in living cells. 206 Later, they proposed a ratiometric Cu + -specific fluorescent probe 87 by employing the same receptor but based on an ICT mechanism ( Figure 13). 207 87 has a K d of 4.0 × 10 −11 M for Cu + and can detect changes in intracellular Cu + concentration upon exogenous copper addition.…”

Section: Complexation-based Chromogenic Andmentioning

confidence: 99%

Design Strategies for Water-Soluble Small Molecular Chromogenic and Fluorogenic Probes

et al. 2013

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“…In this framework we have developed a ratiometric nanosensor exploiting the synergistic contributions of the specific chemosensor designed by Chang et al 25 and of core-shell silica NPs (Fig. 26 The NPs were synthesized by using a micellar system (Pluronic F127) as a template. 26 The NPs were synthesized by using a micellar system (Pluronic F127) as a template.…”

Section: Copper Sensorsmentioning

confidence: 99%

Luminescent chemosensors based on silicananoparticles for the detection of ionic species

et al. 2013

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A Versatile Strategy for Signal Amplification Based on Core/Shell Silica Nanoparticles

Cited by 43 publications

References 30 publications

The Inorganic Side of NGF: Copper(II) and Zinc(II) Affect the NGF Mimicking Signaling of the N-Terminus Peptides Encompassing the Recognition Domain of TrkA Receptor

The Inorganic Side of NGF: Copper(II) and Zinc(II) Affect the NGF Mimicking Signaling of the N-Terminus Peptides Encompassing the Recognition Domain of TrkA Receptor

Design Strategies for Water-Soluble Small Molecular Chromogenic and Fluorogenic Probes

Luminescent chemosensors based on silicananoparticles for the detection of ionic species

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