ArticleThe Journal of biological chemistry2008
Design of a conformationally defined and proteolytically stable circular mimetic of brain-derived neurotrophic factor.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 49 citations in OpenAlex.
- The Selective Glucocorticoid Receptor Modulator Cort125329 Decreases Neuroinflammation and Gliosis and Enhances Myelination in the Wobbler Model of Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2025Article
- Multicomponent synthesis of chromophores - The one-pot approach to functional π-systems.Frontiers in chemistry · 2023Review
- Peptides Derived from Growth Factors to Treat Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Dimeric mimetic of BDNF loop 4 promotes survival of serum-deprived cell through TrkB-dependent apoptosis suppression.Scientific reports · 2021Article
- Therapeutic Targeting Strategies for Early- to Late-Staged Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Article
- Supramolecular Nanostructure Activates TrkB Receptor Signaling of Neuronal Cells by Mimicking Brain-Derived Neurotrophic Factor.Nano letters · 2018Article
- Increased cortical synaptic activation of TrkB and downstream signaling markers in a mouse model of Down Syndrome.Neurobiology of disease · 2015Article
- Neurotrophin strategies for neuroprotection: are they sufficient?Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2014Review
- Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease.Nature reviews. Drug discovery · 2013Review
- BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases.Nature reviews. Neuroscience · 2013Review
- TrkB receptor signalling: implications in neurodegenerative, psychiatric and proliferative disorders.International journal of molecular sciences · 2013Review
- From molecular to nanotechnology strategies for delivery of neurotrophins: emphasis on brain-derived neurotrophic factor (BDNF).Pharmaceutics · 2013Article
- Low molecular weight, non-peptidic agonists of TrkA receptor with NGF-mimetic activity.Cell death & disease · 2012Article
- Brain-derived neurotrophic factor and neuropsychiatric disorders.Pharmacological reviews · 2012Review
- Synthesis of peptide macrocycles using unprotected amino aldehydes.Nature protocols · 2010Article
- Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice.PloS one · 2010Article
- Article
- Brain-derived neurotrophic factor loop 4 dipeptide mimetic GSB-106 activates TrkB, Erk, and Akt and promotes neuronal survival in vitro.Doklady. Biochemistry and biophysicsArticle
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of neurotrophic factors. BDNF has long been recognized to have potential for the treatment of a variety of human neurodegenerative diseases. However, clinical trials with recombinant BDNF have yet to yield success, leading to the suggestion that alternative means of harnessing BDNF actions for therapeutic use may be required. Here we describe an approach to create low molecular weight peptides that, like BDNF, promote neuronal survival. The peptides were designed to mimic a cationic tripeptide sequence in loop 4 of BDNF shown in previous studies to contribute to the binding of BDNF to the common neurotrophin receptor p75NTR. The best of these peptides, the cyclic pentapeptide 2 (cyclo(-D-Pro-Ala-Lys-Arg-)), despite being of low molecular weight (Mr 580), was found to be an effective promoter of the survival of embryonic chick dorsal root ganglion sensory neurons in vitro (maximal survival, 68 +/- 3% of neurons supported by BDNF). Pentapeptide 2 did not affect the phosphorylation of either TrkB (the receptor tyrosine kinase for BDNF) or the downstream signaling molecule MAPK, indicating that its mechanism of neuronal survival action is independent of TrkB. NMR studies reveal that pentapeptide 2 adopts a well defined backbone conformation in solution. Furthermore, pentapeptide 2 was found to be effectively resistant to proteolysis when incubated in a solution of rat plasma in vitro. These properties of pentapeptide 2 (low molecular weight, appropriate pharmacological actions, a well defined solution conformation, and proteolytic stability) render it worthy of further investigation, either as a template for the further design of neuronal survival promoting agents or as a lead compound with therapeutic potential in its own right.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.