Nerve Growth Factor Protects Against Alcohol-Induced Neurotoxicity in PC12 Cells
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            PI3K/Akt/mTOR Pathway

Liu, Liping; Sun, Tiedong; Xin, Feng; Cui, Wei; Guo, Jianquan; Hu, Jianguo

doi:10.1093/alcalc/agw077

Cited by 24 publications

(18 citation statements)

References 40 publications

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“…It is widely known that PI3K/AKT and MAPK/ERK pathways are two major intracellular signaling networks activated by growth factors responsible for the cell survival [18]. It has been reported that NGF mediated neuroprotective signaling is most likely to depend on PI3K/AKT rather than MAPK/ERK pathway [19][20][21]. The results obtained in the current study indicate that selective activation of PI3K/AKT by NGF mimetic is sufficient for the manifestation of neuroprotective activity in vivo.…”

Section: Resultssupporting

confidence: 61%

Dimeric Dipeptide Mimetics of NGF and BDNF Are Promising Agents for Post-Stroke Therapy

Povarnina¹,

Gudasheva²,

Середенин³

2018

JBiSE

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The dimeric dipeptide mimetics of the brain derived neurotrophic factor (BDNF) loops 1 and 4 and nerve growth factor (NGF) loop 4 were designed and synthesized at the Zakusov Research Institute of Pharmacology. There are respectively bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylenediamide (GSB-214), bis-(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide (GSB-106) and bis-(N-monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide (GK-2). All of the obtained compounds activated a corresponding specific NGF or BDNF tyrosine kinase receptor (TrkA or TrkB), but had different postreceptor signaling patterns. GSB-106 activated the ERK and AKT, whereas GSB-214 and GK-2 only activated the AKT kinase. Here we report a comparative analysis of neuroprotective activity of these dipeptides in a model of ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The all three dimeric dipeptides showed a statistically significant decrease of infarct volumes with the treatment beginning 4 hour after surgery. In the experiment with BDNF mimetics, GSB-106 reduced this volume by 66% and GSB-214 by 26%. NGF GK-2 reduced the cerebral infarct volume by 45%. Thus, BDNF mimetic, which activated both the ERK and AKT, and NGF mimetic, which selectively activated PI3K/AKT, showed high neuroprotective efficacy. In addition, we studied neuroprotective effects of GK-2 at the beginning of the treatment 6, 8 and 24 hours after reperfusion. The neuroprotective effect of GK-2 persisted in all these conditions. The effectiveness of GK-2 at a delayed start of administration suggests that the dipeptide has neuroregenerative properties. The results obtained suggest a potential role for the dimeric dipeptide NGF and BDNF mimetics as therapeutic agents useful in the treatment of a stroke.

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Section: Resultssupporting

confidence: 61%

Dimeric Dipeptide Mimetics of NGF and BDNF Are Promising Agents for Post-Stroke Therapy

Povarnina¹,

Gudasheva²,

Середенин³

2018

JBiSE

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“…PI3K/Akt cascade seems to provide trophic support for neurons, block apoptosis, facilitate signal transmission and mediate cell growth and differentiation in neurons. Also, it is reported that NGF is mediated by PI3K/Akt/mTOR pathway [281][282][283]. Ras-ERK pathway is a key promoter of neurite outgrowth and also has been found to enhance axonal survival [284].…”

Section: Pharmacological Agentsmentioning

confidence: 99%

Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

Pedrosa¹,

Caseiro²,

Santos³

et al. 2017

Scaffolds in Tissue Engineering - Materials, Technologies and Clinical Applications

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Human adult peripheral nerve injuries are a high incidence clinical problem that greatly affects patients' quality of life. Although peripheral nervous system has intrinsic regenerative capacity, this occurs in an incomplete or poorly functional manner. When a nerve fiber loses its continuity with consequent damage of the basal lamina tubes, axon spontaneous regeneration is disorganized and mismatched. These phenomena translate in an inadequate nerve functional recovery and consequent musculoskeletal incapacity. Nerve grafts still remain the gold standard in peripheral injuries treatment. However, this approach contains its disadvantages such as the necessity of primary surgery to harvest the autografts, loss of a functional nerve, donor site morbidity and longer surgery procedures. Therefore, biomaterials and tissue engineering can provide efficient resources and alternatives to nerve injury repair not only by the development of biocompatible structures but also, introducing neurotrophic factors and cellular systems to stimulate optimum clinical outcome. In this chapter, a comprehensive state-of-the art picture of tissue-engineered nerve grafts scaffolds, their application in nerve regeneration along with latest advances in peripheral nerve repair and future perspectives will be discussed, including our own large experience in this field of knowledge.

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“…This anti-apoptotic effect of NGF is consistent with previous studies and may improve recovery following SCI. 48,49 Functional recovery is an essential factor for successful SCI treatment. In this study, locomotor function was assessed in rats after SCI.…”

mentioning

confidence: 99%

Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

Song¹,

Wang

Shen³

et al. 2017

IJN

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Background Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. Purpose This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) ( NGF /PLGA NBs) on nerve regeneration in rats following SCI. Materials and methods Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF /PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. Results NGF therapy using US-mediated NGF /PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. Conclusion US-mediated NGF /PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF /PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases.

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Nerve Growth Factor Protects Against Alcohol-Induced Neurotoxicity in PC12 Cells via PI3K/Akt/mTOR Pathway

Abstract: In this study, we chose the PC12 cell line as a neuronal model, and our results demonstrate that nerve growth factor can induce autophagy with the neuroprotective effect and regulatory mechanisms of alcohol-induced autophagy in PC12 cells.

Cited by 24 publications

References 40 publications

Dimeric Dipeptide Mimetics of NGF and BDNF Are Promising Agents for Post-Stroke Therapy

Dimeric Dipeptide Mimetics of NGF and BDNF Are Promising Agents for Post-Stroke Therapy

Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

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