A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic
| Autor: | Bommana Raghunath Reddy, Swati Maitra, Lenin Veeraval, Srihari Pabbaraja, Dwaipayan Bhattacharya, Arvind Kumar, Tapatee Das, Ramesh Samineni, Goverdhan Mehta, Shailaja Karri, Sumana Chakravarty, Abhipradnya Bipin Wahul, Pranav Chintamani Joshi |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Central Nervous System
Male 0301 basic medicine Scaffold Transcription Genetic Neurogenesis Science Pharmacology Neuroprotection Article 03 medical and health sciences 0302 clinical medicine Ischemia In vivo Neurites Animals Spiro Compounds Nerve Growth Factors Protein Kinase Inhibitors Zebrafish Neuroinflammation Inflammation Multidisciplinary Cell Death biology Chemistry Cell Differentiation biology.organism_classification Antidepressive Agents In vitro Mice Inbred C57BL Disease Models Animal Neuroprotective Agents 030104 developmental biology Anti-Anxiety Agents biology.protein Medicine 030217 neurology & neurosurgery Ex vivo Neurotrophin |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Following our recent discovery of a new scaffold exhibiting significant neurotrophic and neurogenic activities, a structurally tweaked analogue, embodying a 2-oxa-spiro [5.4]decane framework, has been conceptualised and found to be more potent and versatile. It exhibits enhanced neurotrophic and neurogenic action in in vitro, ex vivo and in vivo models and also shows robust neuroprotection in mouse acute cerebral stroke model. The observed attributes are traceable to the predominant activation of the TrkB-PI3K-AKT-CREB pathway. In addition, it also exhibits remarkable anti-neuroinflammatory activity by concurrently down-regulating pro-inflammatory cytokines IL-1α and IL-6, thereby providing a unique molecule with a trinity of neuroactivities, i.e. neurotrophic, neurogenic and anti-inflammatory. The new chemical entity disclosed here has the potential to be advanced as a versatile therapeutic molecule to treat stroke, depression, and possibly other neuropsychiatric disorders associated with attenuated neurotrophic/ neurogenic activity, together with heightened neuroinflammation. |
| Databáze: | OpenAIRE |
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