Publication: PROTECTIVE EFFECT OF NEURONAL STEM CELLS (NE4C) AGAINST MICROGLIA-MEDIATED NEUROTOXICITY
| dc.contributor.author | CINDY WONG | |
| dc.date.accessioned | 2023-10-06T15:31:58Z | |
| dc.date.available | 2023-10-06T15:31:58Z | |
| dc.date.issued | 2018-03 | |
| dc.description.abstract | Background: The histopathological hallmarks of Alzheimer’s disease (AD) are aggregation of senile plaques (SPs) and neurofibrillary tangles (NFTs) which resulting in progressive dysfunction of synaptic activity and eventually neurodegeneration. The aggregation of amyloid-β peptides and deposition of tau oligomers contributes to the pathological formation of SPs and NFTs respectively. Besides, neuroinflammation also contribute to pathogenesis and progression of AD. Neural stem cells (NSCs) have the ability to self-proliferate and protect the nervous system. Thus, this regenerative characteristic of NSCs provide great promise in regenerating neuronal cells in the brain for aging, neuroinflammation and neurodegeneration. This study aims to investigate the protective effect of NSCs (NE4C) against microglial-mediated neurotoxicity. Methods: Cell viability assay was used to study the protective effect of NE-4C on the viability of SH-SY5Y. Western blot was used to study the expression of tau and its signalling pathway: glycogen synthase kinase 3β (GSK3β) and p38α mitogen-activated protein kinase (p38α MAPK); also amyloid-β processing protein: amyloid-β precursor protein (APP) and beta-site APP cleaving enzyme 1 (BACE1). The expression of beta-amyloid (Aβ) was determined by enzyme-linked immunosorbent assay (ELISA). Results: The protective effect of NE4C on SH-SY5Y cells against microglia-mediated neurotoxicity was observed in cell viability studies. The expression of phosphorylated tau, Aβ, GSK3β and phosphorylated p38α MAPK in SH-SY5Y cells were downregulated when cultured in the conditioned media of co-culture of NE-4C and BV2 cells. However, LPS stimulation do not affect the expression of APP and BACE1 in SH-SY5Y cells. Co-cultured of NE-4C cells with BV2 cells resulted in decrease in APP and BACE1 expression regardless of microglial activation by LPS. Conclusion: The NE-4C cells confer protective effect on SH-SY5Y cells against microglia-mediated neurotoxicity by suppressing the expression of tau and its signalling pathway. The attenuation of Aβ by NE-4C cells when NE-4C cells co-cultured with BV2 cells were unlikely to be due to the attenuation of APP and BACE1 expression alone. Further studies to determine the mechanisms involved in the attenuation of Aβ by NE4C through regulation of BV2 cells is required. Collectively, these results suggested that the neuroprotective effect of NE4C against microglia-mediated toxicity involved the attenuation of tau phosphorylation and amyloidogenesis, adding to the inherent benefits of NSCs in AD treatment. | en_US |
| dc.identifier.uri | https://hdl.handle.net/20.500.14377/32194 | |
| dc.language.iso | en | en_US |
| dc.publisher | International Medical University | en_US |
| dc.subject | Alzheimer Disease | en_US |
| dc.subject | Plaque, Amyloid | en_US |
| dc.subject | Neurofibrillary Tangles | en_US |
| dc.subject | Neural Stem Cells | en_US |
| dc.subject | Glycogen Synthase Kinases | en_US |
| dc.title | PROTECTIVE EFFECT OF NEURONAL STEM CELLS (NE4C) AGAINST MICROGLIA-MEDIATED NEUROTOXICITY | en_US |
| dc.type | Thesis | |
| dspace.entity.type | Publication |