IMM-H004 reduced okadaic acid-induced neurotoxicity by inhibiting Tau pathology in vitro and in vivo
| Autor: | Yu-Xia Lou, Dan-Dan Liu, Piao Luo, Tian-bi Zhu, Xiuyun Song, Qi Wang, Ying-Ying Wang, Naihong Chen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
Tau protein Blotting Western Morris water navigation task Apoptosis tau Proteins Toxicology Neuroprotection PC12 Cells Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Western blot In vivo Alzheimer Disease Coumarins Okadaic Acid medicine Animals Maze Learning 030304 developmental biology 0303 health sciences biology medicine.diagnostic_test Chemistry General Neuroscience Cyclin-dependent kinase 5 Neurotoxicity Okadaic acid medicine.disease Flow Cytometry Molecular biology Rats Disease Models Animal Neuroprotective Agents nervous system biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Neurotoxicology. 75 |
| ISSN: | 1872-9711 |
| Popis: | This study aimed to explore effects and mechanisms of 004 (IMM-H004), a novel coumarin derivative, in OKA (okadaic acid)-induced AD (Alzheimer's disease)-like model. In vitro, MTT, LDH, and Annexin V/FITC flow cytometry assay were used to test cell survival. In vivo, OKA microinjection was conducted to simulate AD-like neuropathology. Morris water maze and Nissl staining were used to detect spatial memory function and neuronal damage respectively. Western blot and immunohistochemistry were used to study the mechanisms of 004 in Tau pathology. The results showed that 004 reduced cell death and increased survival in PC12 cells, and decreased neuronal injury in the hippocampus in rats. 004 improved learning and memory functions in OKA-treated rats. The mechanistic studies indicated that 004 inhibited phosphorylation of Tau protein by down-regulating the activity of protein kinases CDK5 and GSK3β and increasing PP2A activity. Overall, 004 improved spatial memory impairments and neuron cells injury induced by OKA; on the other hand, 004 inhibited Tau hyperphosphorylation by regulating CDK5, GSK3β and PP2A. |
| Databáze: | OpenAIRE |
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