Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

Keefe, Kathleen M.; Sheikh, Imran S.; Smith, George M.

doi:10.3390/ijms18030548

Cited by 259 publications

(199 citation statements)

References 166 publications

(210 reference statements)

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“…This data is in line with previous observations that local NGF actions account for axon elongation 25 . Indeed, NGF-induced axonal sprouting in sensory neurons has been widely investigated, and NGF treatment probed in models of spinal cord injury 49 . Several aspects still need to be addressed, e.g.…”

Section: Resultsmentioning

confidence: 99%

Graphene Promotes Axon Elongation through Local Stall of Nerve Growth Factor Signaling Endosomes

et al. 2020

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Several works reported increased differentiation of neuronal cells grown on graphene; however, the molecular mechanism driving axon elongation on this material has remained elusive. Here, we study the axonal transport of nerve growth factor (NGF), the neurotrophin supporting development of peripheral neurons, as a key player in the time course of axonal elongation of dorsal root ganglion neurons on graphene. We find that graphene drastically reduces the number of retrogradely transported NGF vesicles in favor of a stalled population in the first two days of culture, in which the boost of axon elongation is observed. This correlates with a mutual charge redistribution, observed via Raman spectroscopy and electrophysiological recordings. Furthermore, ultrastructural analysis indicates a reduced microtubule distance and an elongated axonal topology. Thus, both electrophysiological and structural effects can account for graphene action on neuron development. Unraveling the molecular players underneath this interplay may open new avenues for axon regeneration applications.

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Section: Resultsmentioning

confidence: 99%

Graphene Promotes Axon Elongation through Local Stall of Nerve Growth Factor Signaling Endosomes

et al. 2020

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“…Our study indicated that AG1601 suppressed the proliferation of C6 glioma cells with dose and time dependence in vitro (Figure ). BDNF/TrkB/PI3k/Akt signal has great effects on the regulation of growth, development, and regeneration in neurons . Moreover, BDNF/TrkB/PI3K/Akt signal also could regulate the proliferation, apoptosis, invasion, and migration of many kinds of cancer cells, including breast cancer, multiple myeloma, and bladder tumor .…”

Section: Discussionmentioning

confidence: 99%

“…BDNF/TrkB/PI3k/Akt signal has great effects on the regulation of growth, development, and regeneration in neurons. 12,21 Moreover, BDNF/TrkB/PI3K/Akt signal also could regulate the proliferation, apoptosis, invasion, and migration of . BDNF, brain-derived neurotrophic factor; PI3K, phosphatidylinositol-3 kinases; TrkB, tropomyosin-related kinase B many kinds of cancer cells, including breast cancer, 23 multiple myeloma, 24 and bladder tumor.…”

Section: Discussionmentioning

confidence: 99%

The inhibition of BDNF/TrkB/PI3K/Akt signal mediated by AG1601 promotes apoptosis in malignant glioma

Yin

Jiang

Yinguo

et al. 2019

J of Cellular Biochemistry

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Malignant glioma is the most aggressive primary brain tumor and has a poor survival rate. Even if extensive methods are preformed to treat glioma, the mortality rate is still very high. It is necessary for discovering and developing new drugs for malignant glioma treatment. AG1601 is one of AG‐series drugs, including AG1031 and AG1503, and it has been optimized on the original basis. In our study, we found that AG1601 markedly inhibited proliferation and promoted C6 glioma cell apoptosis in vitro. AG1601 also reduced the size and weight of glioma in vivo. The growth ability of glioma was significantly inhibited after treatment with AG1601. It also showed that the expression levels of BDNF/TrkB/PI3K/Akt signal related proteins were obviously decreased in C6 glioma cells after treatment with AG1601 in vivo and in vitro. We also found that BDNF, as the activator of BDNF/TrkB/PI3K/Akt signal, reversed the anti‐proliferation and pro‐apoptosis of C6 glioma cells caused by AG1601. K252a, a specific inhibitor of TrkB, and AG1601 in combination aggravated C6 glioma cell apoptosis. These results indicate that AG1601 has good effects on the anti‐proliferation and pro‐apoptosis of malignant glioma via BDNF/TrkB/PI3K/Akt signal and could be considered as a potential drug in treating malignant glioma.

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“…Controlled release of a biomolecule payload is of interest for inducing, enhancing, or selectively inhibiting cell growth along tissue scaffolds, and this is of particular interest in neuronal regeneration. [72] Protein-based therapeutics have posed one of the longstanding challenges in the area of drug eluting polymers, because the processing conditions used to prepare many bioresorbable polymer systems are incompatible with proteins, and the protein is often extensively denatured or hydrolyzed during formulation or during release. [73–74] For these experiments we used lysozyme as a test protein because there is a standard and sensitive assay for lysozyme activity that allows convenient quantification of denaturation or other degradative processes that the protein might undergo.…”

mentioning

confidence: 99%

Oriented Nanofibrous Polymer Scaffolds Containing Protein‐Loaded Porous Silicon Generated by Spray Nebulization

et al. 2018

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Oriented composite nanofibers consisting of porous silicon nanoparticles (pSiNPs) embedded in a polycaprolactone or poly(lactide-co-glycolide) matrix are prepared by spray nebulization from chloroform solutions using an airbrush. The nanofibers can be oriented by an appropriate positioning of the airbrush nozzle, and they can direct growth of neurites from rat dorsal root ganglion neurons. When loaded with the model protein lysozyme, the pSiNPs allow the generation of nanofiber scaffolds that carry and deliver the protein under physiologic conditions (phosphate-buffered saline (PBS), at 37 °C) for up to 60 d, retaining 75% of the enzymatic activity over this time period. The mass loading of protein in the pSiNPs is 36%, and in the resulting polymer/pSiNP scaffolds it is 3.6%. The use of pSiNPs that display intrinsic photoluminescence (from the quantum-confined Si nanostructure) allows the polymer/pSiNP composites to be definitively identified and tracked by time-gated photoluminescence imaging. The remarkable ability of the pSiNPs to protect the protein payload from denaturation, both during processing and for the duration of the long-term aqueous release study, establishes a model for the generation of biodegradable nanofiber scaffolds that can load and deliver sensitive biologics.

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Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

Cited by 259 publications

References 166 publications

Graphene Promotes Axon Elongation through Local Stall of Nerve Growth Factor Signaling Endosomes

Graphene Promotes Axon Elongation through Local Stall of Nerve Growth Factor Signaling Endosomes

The inhibition of BDNF/TrkB/PI3K/Akt signal mediated by AG1601 promotes apoptosis in malignant glioma

Oriented Nanofibrous Polymer Scaffolds Containing Protein‐Loaded Porous Silicon Generated by Spray Nebulization

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