Molecular Basis of Neurotrophin—Receptor Interactions

Pattarawarapan, Mookda; Burgess, Kevin

doi:10.1002/chin.200411274

Cited by 15 publications

(46 citation statements)

References 1 publication

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“…This region is located in the fifth subdomain of the extracellular domain of TrkB and has been described as the "specificity patch" of the receptor, as it interacts with the N-terminal region of BDNF (26,28). In fact, the N-terminal end of neurotrophins has been shown (a) to be highly variable in terms of amino acid composition, (b) to affect Trk receptor binding and activation capacities, and (c) to fit into a binding pocket formed by a patch of charged amino acids in the fifth subdomain of Trk receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Modeling of ANA-12 docking in the specificity patch showed that the molecule nicely fits into the TrkB-d5 ADEB β-sheet and behaves like the N terminus region of BDNF in the binding pocket (26,28). Similarly to NT-4/5 and BDNF, ANA-12 lies against the disulfide bridge formed by Cys302 and Cys347 and interacts with Asp298, His299, and His300.…”

Section: Figurementioning

confidence: 99%

“…26,27). Moreover, the crystal structure of NT-4/5 in complex with the fifth subdomain of TrkB (TrkB-d5) shows that the N-terminal region of the neurotrophin interacts with the "specificity patch" of the receptor, a binding pocket located in TrkB-d5 that is thought to drive the selectivity of the interaction with BDNF ( Figure 1).…”

Section: Modeling Of the Bdnf/trkb Specificity Patch And Docking-basementioning

confidence: 99%

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Identification of a low–molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice

Cazorla

Prémont²,

Mann³

et al. 2011

J. Clin. Invest.

341

315

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Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Modeling Of the Bdnf/trkb Specificity Patch And Docking-basementioning

confidence: 99%

See 1 more Smart Citation

Identification of a low–molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice

Cazorla

Prémont²,

Mann³

et al. 2011

J. Clin. Invest.

341

315

View full text Add to dashboard Cite

“…It is well known that TrkB belongs to a large group of tyrosine-kinase receptors, and BDNF as well as NT-4 are the only ligands for this receptor. 21 The human TrkB is a transmembrane glycoprotein type I that consists of 792 AA residues. Its extracellular domain comprises of three tandem leucine-rich motifs, bordered by two cysteine clusters, and trailed by two immunoglobulin (Ig)-like domains, Ig 1 and Ig 2 , 35 where Ig 2 , the closest to cell membrane, is the binding site for BDNF.…”

Section: Bdnf Receptorsmentioning

confidence: 99%

“…20 The three-dimensional molecular structure of BDNF appears to be a homodimer with noncovalent bonds, where each monomer consists of three pairs of anti-parallel β-sheets connected to four loops of β-strands containing 3 disulfide bonds with cysteine knot motif. 21 Besides, the crystallographic BDNF structure is shown in protein databases as heterodimers with NT-3 (code 1B8M) and NT-4 (code 1BND). 22,23 The BDNF human gene is mapped on chromosome 11 between 11p13 and 11p14.…”

Section: Introductionmentioning

confidence: 99%

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Khalin¹,

Alyautdin²,

Kocherga³

et al. 2015

IJN

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Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood–retinal barrier and blood–cochlear barrier, which have a comparable structure to the blood–brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration.

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The trophic effect of nerve growth factor in primary cultures of rat hippocampal neurons is associated to an anti‐inflammatory and immunosuppressive transcriptional program

Maino

Spampinato

Severini

et al. 2018

Journal Cellular Physiology

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Nerve growth factor, the prototype of a family of neurotrophins, elicits differentiation and survival of peripheral and central neuronal cells. Although its neural mechanisms have been studied extensively, relatively little is known about the transcriptional regulation governing its effects. We have previously observed that in primary cultures of rat hippocampal neurons treatment with nerve growth factor for 72 hr increases neurite outgrowth and cell survival. To obtain a comprehensive view of the underlying transcriptional program, we performed whole-genome expression analysis by microarray technology. We identified 541 differentially expressed genes and characterized dysregulated pathways related to innate immunity: the complement system and neuro-inflammatory signaling. The exploitation of such genes and pathways may help interfering with the intracellular mechanisms involved in neuronal survival and guide novel therapeutic strategies for neurodegenerative diseases.

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Molecular Basis of Neurotrophin—Receptor Interactions

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 15 publications

References 1 publication

Identification of a low–molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice

Identification of a low–molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

The trophic effect of nerve growth factor in primary cultures of rat hippocampal neurons is associated to an anti‐inflammatory and immunosuppressive transcriptional program

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