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Investigating the effect of ceramide synthesis inhibition on hippocampal neurons exposed to Aβ
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Pegah Javadpour   , Sahar Askari , Rasoul Ghasemi |
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Abstract: (285 Views) |
Introduction: Despite the high prevalence of Alzheimer's disease (AD) in recent years, the main cause and therefore the appropriate treatment for these patients is still unknown. Disruption of sphingolipids metabolism and increase in ceramide levels have been reported in the affected areas of the brain. According to the involvement of ceramide in cell death shown mostly in peripheral organs, we aimed that inhibition of ceramide synthesis in one pathway can protect neurons against Aβ toxicity. In this study, serine palmitoyl transferase (SPT), rate liming enzyme of the denovo synthesis pathway was targeted and caspase-3 activity was investigated in isolated hippocampal cells.
Methods and Materials: The embryonic hippocampal cells were obtained from 18–19 day rat embryos. The cells were exposed to Aβ25−35 (10 μM) in the absence or presence of myriocin (50 nM and 1µM) as SPT inhibitor for 24 hours. After that, MTT assay and Western blot were done.
Results: Myriocin at the dose of 1 µM significantly prevented the cell loss and caspase-3 cleavage caused by Aβ25−35.
Conclusion: These results imply that preventing the increase of ceramide in the cell, even partly, can protect cells against Aβ25-35 toxicity. So, targeting ceramide synthesis pathways besides other protective and treatment strategies might be helpful in AD.
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| Keywords: Alzheimer's Disease, Amyloid beta-Peptides, Ceramide, Cell Death, Myriocin |
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Full-Text [PDF 382 kb]
(41 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2023/12/29 | Accepted: 2023/08/23 | Published: 2023/08/23
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