A network map of BDNF/TRKB and BDNF/p75NTR signaling system

Sandhya, Varot K.; Raju, Rajesh; Verma, Renu; Advani, Jayshree; Sharma, Rakesh; Radhakrishnan, Aneesha; Nanjappa, Vishalakshi; Jayasuryan, Narayana; Somani, Babu Lal; Mukherjee, Kanchan Kumar; Pandey, Akhilesh; Christopher, Rita; Prasad, T. S. Keshava

doi:10.1007/s12079-013-0200-z

Cited by 73 publications

(51 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Brain-derived neurotrophic factor (BDNF) is a member of family of neurotrophins that plays a major role in the growth, differentiation, plasticity and survival of neurons. BDNF is also involved in the biological processes such as energy metabolism, mental health, behavior, learning, memory, stress, pain and apoptosis2930. The predicted activation/inhibition relationships in the BDNF signalling pathway are illustrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

Multi-label ℓ2-regularized logistic regression for predicting activation/inhibition relationships in human protein-protein interaction networks

Mei

Zhang

2016

Sci Rep

View full text Add to dashboard Cite

Protein-protein interaction (PPI) networks are naturally viewed as infrastructure to infer signalling pathways. The descriptors of signal events between two interacting proteins such as upstream/downstream signal flow, activation/inhibition relationship and protein modification are indispensable for inferring signalling pathways from PPI networks. However, such descriptors are not available in most cases as most PPI networks are seldom semantically annotated. In this work, we extend ℓ2-regularized logistic regression to the scenario of multi-label learning for predicting the activation/inhibition relationships in human PPI networks. The phenomenon that both activation and inhibition relationships exist between two interacting proteins is computationally modelled by multi-label learning framework. The problem of GO (gene ontology) sparsity is tackled by introducing the homolog knowledge as independent homolog instances. ℓ2-regularized logistic regression is accordingly adopted here to penalize the homolog noise and to reduce the computational complexity of the double-sized training data. Computational results show that the proposed method achieves satisfactory multi-label learning performance and outperforms the existing phenotype correlation method on the experimental data of Drosophila melanogaster. Several predictions have been validated against recent literature. The predicted activation/inhibition relationships in human PPI networks are provided in the supplementary file for further biomedical research.

show abstract

Section: Resultsmentioning

confidence: 99%

Multi-label ℓ2-regularized logistic regression for predicting activation/inhibition relationships in human protein-protein interaction networks

Mei

Zhang

2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Nevertheless, no experiments have been conducted to investigate role of TrkB signalling in the inflammatory response following TBI. In fact, BDNF acts as a dimer to be combined with the TrkB tyrosine kinase receptor, leading to autophosphorylation and activation of downstream pathways . Considering that BDNF binds to TrkB receptors through different signal pathways to regulate neuronal survival and cell migration, we performed Western blot to detect the expression of STAT6, NF‐κB and TrkB.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, BDNF acts as a dimer to be combined with the TrkB tyrosine kinase receptor, leading to autophosphorylation and activation of downstream pathways. [29] Considering that BDNF binds to TrkB receptors through different signal pathways to regulate neuronal survival and cell migration, we performed Western blot to detect the expression of STAT6, NF-jB and TrkB. STAT6 signalling is widely involved in cell proliferation, differentiation and immune regulation, which is a vital pathway for inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor fused with a collagen-binding domain inhibits neuroinflammation and promotes neurological recovery of traumatic brain injury mice via TrkB signalling

Yin

Zhao

Qiu

2020

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Objectives As one of the vital nutrient factors in central nervous system (CNS), brain‐derived neurotrophic factor (BDNF) can significantly attenuate neuron damage and promote neurogenesis. Nevertheless, little research has been conducted on regulating the effect of BDNF on the inflammatory response after traumatic brain injury (TBI). Methods In this study, we used BDNF fused with a collagen‐binding domain (CBD‐BDNF) to maintain a sufficient concentration of BDNF in the TBI hemisphere, and then, the regulatory effects of BDNF and CBD‐BDNF on the inflammatory response of microglia were investigated both on a TBI mice model in vivo and LPS‐stimulated microglia experiment in vitro. Key findings The results revealed that BDNF and CBD‐BDNF had similar effects on attenuating the pro‐inflammatory reactions but promoting anti‐inflammatory responses of microglia induced by LPS in vitro. Furthermore, CBD‐BDNF significantly improved the neurological behaviours of TBI mice and alleviated the inflammatory reaction after TBI, while BDNF had weaker effects compared with those of CBD‐BDNF. Additionally, the TrkB inhibitor K252a significantly inhibited the above effects of CBD‐BDNF. Conclusions In conclusion, CBD‐BDNF can promote the anti‐inflammatory function of microglia and neurological recovery of TBI mice through TrkB signalling.

show abstract

“…It acts mainly through binding to TrkB receptors, leading to receptor dimerization, kinase activation and autophosphorylation, adaptor protein recruitment, and ultimately the activation of PI3K/Akt, MAPK/ERK, Jak/Stat, PLC/PKC, NFκB and RAS/ERK pathways, amongst many others. The extensive BDNF signaling pathways are summarized by Sandhya and colleagues (2013), with crucial roles in all neuron developmental processes [94][95][96][97] . Its actions through the JAK/STAT pathway result in neurite outgrowth 94 , while neurogenesis requires its activation of MAPK/ERK signaling 95 , and its neuronal progeny are typically dopaminergic 98 or GABAergic 99 neurons.…”

Section: 3b -Bdnfmentioning

confidence: 99%

“…The extensive BDNF signaling pathways are summarized by Sandhya and colleagues (2013), with crucial roles in all neuron developmental processes [94][95][96][97] . Its actions through the JAK/STAT pathway result in neurite outgrowth 94 , while neurogenesis requires its activation of MAPK/ERK signaling 95 , and its neuronal progeny are typically dopaminergic 98 or GABAergic 99 neurons. Intraventricular injections of BDNF into rat brains induces neurogenesis and dendrite and axon branching 100 in numerous brain regions, including from ependymal cells in the SVZ 101 and granule cells of the dentate gyrus 102,103 .…”

Section: 3b -Bdnfmentioning

confidence: 99%

Electrophysiological Profile of Differentiating Human Central Canal Ependymal Stem-Progenitor Cells

Malone¹

View full text Add to dashboard Cite

Following spinal cord injury (SCI), current treatments look to halt the spread of tissue damage to minimize pain, with limited effectiveness. Unfortunately, there is no widely used approach for promoting re-growth across the lesion site, a necessity for functional recovery. To that end, stem cell transplant and niche manipulation therapies are a promising tool for repairing damage from SCI and other neurodegenerative conditions. As most stem cell studies are based exclusively on animal models, we aimed to address several gaps in understanding that are fundamental for potential translation to humans. Since immunocytochemistry alone cannot adequately determine whether stem cells have differentiated into mature neurons, we used patchclamp electrophysiology to assess the passive and active electrical properties of stem cells from the central canal of the spinal cord throughout the in vitro differentiation process. Rat ependymal-stem progenitor cells (epSPCs) differentiate towards a majority astrocytic fate under intrinsic differentiation conditions in vitro. Human epSPCs, on the other hand, differentiate towards a majority neuronal fate. Electrophysiological recordings of these cells in intrinsic FBScontaining differentiation media and under BDNF-, GDNF-and RA-guided differentiation show no action potential firing from two to ten weeks in vitro. Passive membrane properties fail to reach that of typical mature neurons within this time frame. Surprisingly, the vast majority of cells showed voltage-dependent spontaneous synaptic currents with reversal near 0 mV, outward rectification, and decay kinetics that are consistent with excitatory glutamatergic responses. Further studies investigating the necessary timeline and the most effective differentiation media required for development of active membrane properties are needed, as is identification of the receptor subtypes responsible for the observed synaptic currents. This will help inform future transplant and stem cell niche manipulation strategies for the treatment of human neurological disorders.iii

show abstract

A network map of BDNF/TRKB and BDNF/p75NTR signaling system

Cited by 73 publications

References 98 publications

Multi-label ℓ2-regularized logistic regression for predicting activation/inhibition relationships in human protein-protein interaction networks

Multi-label ℓ2-regularized logistic regression for predicting activation/inhibition relationships in human protein-protein interaction networks

Brain-derived neurotrophic factor fused with a collagen-binding domain inhibits neuroinflammation and promotes neurological recovery of traumatic brain injury mice via TrkB signalling

Electrophysiological Profile of Differentiating Human Central Canal Ependymal Stem-Progenitor Cells

Contact Info

Product

Resources

About