PUBLICATION
A novel natural product inspired scaffold with robust neurotrophic, neurogenic and neuroprotective action
- Authors
- Chakravarty, S., Maitra, S., Reddy, R.G., Das, T., Jhelum, P., Kootar, S., Rajan, W.D., Samanta, A., Samineni, R., Pabbaraja, S., Kernie, S.G., Mehta, G., Kumar, A.
- ID
- ZDB-PUB-150923-2
- Date
- 2015
- Source
- Scientific Reports 5: 14134 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Zebrafish
- MAP Kinase Signaling System/drug effects
- Azepines/pharmacology
- Extracellular Signal-Regulated MAP Kinases/metabolism
- Brain-Derived Neurotrophic Factor/metabolism
- Receptor, trkB/metabolism
- Neurodegenerative Diseases/drug therapy*
- Neurodegenerative Diseases/prevention & control
- Nerve Growth Factors/antagonists & inhibitors
- Nerve Growth Factors/therapeutic use*
- Neuroprotective Agents/antagonists & inhibitors
- Neuroprotective Agents/therapeutic use*
- Male
- Benzamides/pharmacology
- Disease Models, Animal
- Flavonoids/pharmacology
- Animals
- Mental Disorders/drug therapy*
- Mental Disorders/prevention & control
- Cell Line
- Mice, Inbred C57BL
- Receptors, Nerve Growth Factor/metabolism
- Drug Discovery
- Neurons/metabolism
- Mice
- PubMed
- 26388493 Full text @ Sci. Rep.
Citation
Chakravarty, S., Maitra, S., Reddy, R.G., Das, T., Jhelum, P., Kootar, S., Rajan, W.D., Samanta, A., Samineni, R., Pabbaraja, S., Kernie, S.G., Mehta, G., Kumar, A. (2015) A novel natural product inspired scaffold with robust neurotrophic, neurogenic and neuroprotective action. Scientific Reports. 5:14134.
Abstract
In search for drugs to treat neuropsychiatric disorders wherein neurotrophic and neurogenic properties are affected, two neurotrophically active small molecules specially crafted following natural product leads based on 2-oxa-spiro[5.5]-undecane scaffold, have been thoroughly evaluated for their neurotrophic, neurogenic and neuroprotective potential in ex vivo primary culture and in vivo zebrafish and mouse models. The outcome of in vivo investigations suggest that one of these molecules is more neurotrophic than neurogenic while the other one is more neurogenic than neurotrophic and the former exhibits remarkable neuroprotection in a mouse acute ischemic stroke model. The molecular mechanisms of action of these compounds appear to be through the TrkB-MEK-ERK-CREB-BDNF pathway as pre-treatment with neurotrophin receptor TrkB inhibitor ANA-12 and MEK inhibitor PD98059 attenuates the neurotrophic action of compounds.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping