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Neuroprotective effects of ZL006 in Aβ1–42-treated neuronal cells
- Source :
- Neural Regeneration Research, Neural Regeneration Research, Vol 15, Iss 12, Pp 2296-2305 (2020)
- Publication Year :
- 2020
- Publisher :
- Wolters Kluwer - Medknow, 2020.
-
Abstract
- Amyloid beta (Aβ)-induced neurotoxicity and oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease (AD). ZL006 is shown to reduce over-produced nitric oxide and oxidative stress in ischemic stroke by interrupting the interaction of neuronal nitric oxide synthase and postsynaptic density protein 95. However, few studies are reported on the role of ZL006 in AD. To investigate whether ZL006 exerted neuroprotective effects in AD, we used Aβ1–42 to treat primary cortical neurons and N2a neuroblastoma cells as an in vitro model of AD. Cortical neurons were incubated with ZL006 or dimethyl sulfoxide for 2 hours and treated with Aβ1–42 or NH3•H2O for another 24 hours. The results of cell counting Kit-8 (CCK-8) assay and calcein-acetoxymethylester/propidium iodide staining showed that ZL006 pretreatment rescued the neuronal death induced by Aβ1–42. Fluorescence and western blot assay were used to detect oxidative stress and apoptosis-related proteins in each group of cells. Results showed that ZL006 pretreatment decreased neuronal apoptosis and oxidative stress induced by Aβ1–42. The results of CCK8 assay showed that inhibition of Akt or NF-E2-related factor 2 (Nrf2) in cortical neurons abolished the protective effects of ZL006. Moreover, similar results were also observed in N2a neuroblastoma cells. ZL006 inhibited N2a cell death and oxidative stress induced by Aβ1–42, while inhibition of Akt or Nrf2 abolished the protective effect of ZL006. These results demonstrated that ZL006 reduced Aβ1–42-induced neuronal damage and oxidative stress, and the mechanisms might be associated with the activation of Akt/Nrf2/heme oxygenase-1 signaling pathways.
- Subjects :
- 0301 basic medicine
Amyloid beta
Pharmacology
medicine.disease_cause
Neuroprotection
lcsh:RC346-429
Nrf2
Nitric oxide
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Developmental Neuroscience
neurotoxicity
medicine
oxidative stress
Propidium iodide
Protein kinase B
akt
alzheimer’s disease
amyloid-beta
apoptosis
heme oxygenase-1
nrf2
treatment
zl006
lcsh:Neurology. Diseases of the nervous system
ZL006
biology
Akt
Neurotoxicity
Alzheimer's disease
medicine.disease
N2a cell
030104 developmental biology
chemistry
biology.protein
030217 neurology & neurosurgery
Oxidative stress
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 18767958 and 16735374
- Volume :
- 15
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Neural Regeneration Research
- Accession number :
- edsair.doi.dedup.....a3ae309d48e1b30afd33192d5e6cf27d