Nerve growth factor: basic studies and possible therapeutic applications

Manni, Luigi; Rocco, M. Di; Bianchi, Patrizia; Soligo, Marzia; Guaragna, Morena; Barbaro, Samuele Paparo; Aloe, Luigi

doi:10.3109/08977194.2013.804073

Cited by 81 publications

(55 citation statements)

References 92 publications

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“…As a member of neurotrophic factors, NGF was discovered as a molecule that stimulates the survival and maturation of developing neurons in the peripheral nervous system and has later been shown to protect adult neurons in the degenerating mammalian brain [34,35]. Zhang et al demonstrated that treatment with recombinant DNA vaccine promotes functional recovery in spinal cord hemisected adult rats, associated with expression of endogeous NGF significantly upregulated [36].…”

Section: Discussionmentioning

confidence: 99%

Nerve growth factor improves functional recovery by inhibiting endoplasmic reticulum stress-induced neuronal apoptosis in rats with spinal cord injury

Zhang

Kong

et al. 2014

J Transl Med

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BackgroundEndoplasmic reticulum (ER) stress-induced apoptosis plays a major role in various diseases, including spinal cord injury (SCI). Nerve growth factor (NGF) show neuroprotective effect and improve the recovery of SCI, but the relations of ER stress-induced apoptosis and the NGF therapeutic effect in SCI still unclear.MethodsYoung adult female Sprague-Dawley rats’s vertebral column was exposed and a laminectomy was done at T9 vertebrae and moderate contusion injuries were performed using a vascular clip. NGF stock solution was diluted with 0.9% NaCl and administered intravenously at a dose of 20 μg/kg/day after SCI and then once per day until they were executed. Subsequently, the rats were executed at 1d, 3 d, 7d and 14d. The locomotor activities of SCI model rats were tested by the 21-point Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test and footprint analysis. In addition, Western blot analysis was performed to identify the expression of ER-stress related proteins including CHOP, GRP78 and caspase-12 both in vivo and in vitro. The level of cell apoptosis was determined by TUNEL in vivo and Flow cytometry in vitro. Relative downstream signals Akt/GSK-3β and ERK1/2were also analyzed with or without inhibitors in vitro.ResultsOur results demonstrated that ER stress-induced apoptosis was involved in the injury of SCI model rats. NGF administration improved the motor function recovery and increased the neurons survival in the spinal cord lesions of the model rats. NGF decreases neuron apoptosis which measured by TUNEL and inhibits the activation of caspase-3 cascade. The ER stress-induced apoptosis response proteins CHOP, GRP78 and caspase-12 are inhibited by NGF treatment. Meanwhile, NGF administration also increased expression of growth-associated protein 43 (GAP43). The administration of NGF activated downstream signals Akt/GSK-3β and ERK1/2 in ER stress cell model in vitro.ConclusionThe neuroprotective role of NGF in the recovery of SCI is related to the inhibition of ER stress-induced cell death via the activation of downstream signals, also suggested a new trend of NGF translational drug development in the central neural system injuries which involved in the regulation of chronic ER stress.

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Section: Discussionmentioning

confidence: 99%

Nerve growth factor improves functional recovery by inhibiting endoplasmic reticulum stress-induced neuronal apoptosis in rats with spinal cord injury

Zhang

Kong

et al. 2014

J Transl Med

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“…Western blot densitometry data (n ¼4) were obtained by normalization of the single specific proNGF band with respective GAPDH band and expressed as percentage of control group. Korsching et al, 1985;Seiler and Schwab, 1984) and evidence that this neuronal system is affected early in AD patients (Cuello et al, 2010;Hefti and Weiner, 1986;Olson, 1993) -as well as in experimental models of DE (Rocco et al, 2013;Sposato et al, 2007) -led scientists and clinicians to hypothesize that NGF represents a feasible therapeutic target for diseases characterized by cholinergic neurodegeneration (recently reviewed in: Aloe et al, 2012;Manni et al, 2013). As it has been found that the precursor form of NGF (proNGF) acts as a distinct ligand by binding to a receptor complex consisting of the p75 NTR and sortilin to initiate cell death (Hempstead, 2014;Jansen et al, 2007;Nykjaer et al, 2004), it has been suggested that different neurodegenerative pathologies may be characterized by an abnormal mNGF/proNGF ratio.…”

Section: Discussionmentioning

confidence: 97%

The mature/pro nerve growth factor ratio is decreased in the brain of diabetic rats: Analysis by ELISA methods

et al. 2015

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“…Neverthless, the main culprit in Alzheimer’s disease is the precursor form of NGF, pro-NGF that binds to a sortilin-p75 NTR complex and activates cell death through the stimulation of Jun N-terminal kinase [28]. It’s been demonstrated that pro-NGF is copious in brains of patients with Alzheimer’s disease and this increase may reflect either an active role for proNGF or posttranslational disorders in NGF biosynthesis that reduce the processing of pro-NGF to NGF in Alzheimer’s disease [29].…”

Section: Discussionmentioning

confidence: 99%

Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages

et al. 2017

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PurposeTo investigate the serum levels of Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in patients affected by primary open angle glaucoma with a wide spectrum of disease severity compared to healthy controls and to explore their relationship with morphological and functional glaucoma parameters.Materials and Methods45 patients affected by glaucoma at different stages and 15 age-matched healthy control subjects underwent visual field testing, peripapillary retinal nerve fibre layer thickness measurement using Spectral Domain Optical Coherence Tomography and blood collection for both neurotrophins detection by Enzyme-Linked Immunosorbent Assay. Statistical analysis and association between biostrumental and biochemical data were investigated.ResultsSerum levels of BDNF in glaucoma patients were significantly lower than those measured in healthy controls (261.2±75.0 pg/ml vs 313.6±79.6 pg/ml, p = 0.03). Subgroups analysis showed that serum levels of BDNF were significantly lower in early (253.8±40.7 pg/ml, p = 0.019) and moderate glaucoma (231.3±54.3 pg/ml, p = 0.04) but not in advanced glaucoma (296.2±103.1 pg/ml, p = 0.06) compared to healthy controls.Serum levels of NGF in glaucoma patients were significantly lower than those measured in the healthy controls (4.1±1 pg/mL vs 5.5±1.2 pg/mL, p = 0.01). Subgroups analysis showed that serum levels of NGF were significantly lower in early (3.5±0.9 pg/mL, p = 0.0008) and moderate glaucoma (3.8±0.7 pg/ml, p<0.0001) but not in advanced glaucoma (5.0±0.7 pg/ml, p = 0.32) compared to healthy controls.BDNF serum levels were not related to age, visual field mean deviation or retinal nerve fibre layer thickness either in glaucoma or in controls while NGF levels were significantly related to visual field mean deviation in the glaucoma group (r2 = 0.26, p = 0.004).ConclusionsBDNF and NGF serum levels are reduced in the early and moderate glaucoma stages, suggesting the possibility that both factors could be further investigated as potential circulating biomarkers for the early detection of glaucoma.

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Nerve growth factor: basic studies and possible therapeutic applications

Cited by 81 publications

References 92 publications

Nerve growth factor improves functional recovery by inhibiting endoplasmic reticulum stress-induced neuronal apoptosis in rats with spinal cord injury

Nerve growth factor improves functional recovery by inhibiting endoplasmic reticulum stress-induced neuronal apoptosis in rats with spinal cord injury

The mature/pro nerve growth factor ratio is decreased in the brain of diabetic rats: Analysis by ELISA methods

Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages

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