Abstract
Background: Amyloid-beta (Aβ) induced mitochondrial dysfunction is one of the major causes of neuronal toxicity in Alzheimer’s disease. A number of recent reports suggest involvement of mitochondrial alterations through intracellular accumulation of oligomeric Aβ. These mitochondrial alterations include increased Reactive Oxygen Species (ROS), mt-DNA depletion, decreased oxidative phosphorylation and ATP production, membrane depolarization, reduced number of mitochondria etc. All these defects cumulatively caused neural toxicity and alterations in cellular energy homeostasis. On the other hand, anti-inflammatory drug aspirin is reported to promote both mitochondrial biogenesis and improvement in cellular energy status.
Methods: Taking altogether the mentioned clues, we evaluated protective effect of aspirin, if any on oligomeric Aβ42 induced toxicity and mitochondrial alterations in differentiated neuronal cells. Results: A significant reduction in neuronal viability and increased apoptosis was observed in Aβ42 treated cells, as evident by MTT assay, apoptosis ELISA and immunofluorescence from β-III tubulin antibody staining of neuronal cells. A concomitant decrease was also observed in the intensity of mitotracker red FM staining and mt-DNA to nDNA ratio, suggesting mitochondrial membrane depolarization and/or reduced number of mitochondria along with depletion in mt-DNA. However, simultaneous treatment of 5 μM aspirin to oligomeric Aβ42 treated cells protected them from mitochondrial dysfunction and neurotoxicity. Conclusion: We suggest mitochondrial biogenesis, changes in mitochondrial membrane potential and / or inhibition of Aβ42 aggregation by aspirin as possible underlying mechanism(s).Keywords: Aspirin, oligomeric-Aβ42, EC P19 cells, mitochondrial dysfunction, neurotoxicity, mt-DNA/nDNA.
Current Alzheimer Research
Title:Protective Effect of Aspirin Against Oligomeric Aβ42 Induced Mitochondrial Alterations and Neurotoxicity in Differentiated EC P19 Neuronal Cells
Volume: 14 Issue: 8
Author(s): Hamendra Singh Parmar*, Zbynek Houdek, Martin Pesta, Cerna Vaclava, Pavel Dvorak and Jiri Hatina
Affiliation:
- School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore- 452001, M.P.,India
Keywords: Aspirin, oligomeric-Aβ42, EC P19 cells, mitochondrial dysfunction, neurotoxicity, mt-DNA/nDNA.
Abstract: Background: Amyloid-beta (Aβ) induced mitochondrial dysfunction is one of the major causes of neuronal toxicity in Alzheimer’s disease. A number of recent reports suggest involvement of mitochondrial alterations through intracellular accumulation of oligomeric Aβ. These mitochondrial alterations include increased Reactive Oxygen Species (ROS), mt-DNA depletion, decreased oxidative phosphorylation and ATP production, membrane depolarization, reduced number of mitochondria etc. All these defects cumulatively caused neural toxicity and alterations in cellular energy homeostasis. On the other hand, anti-inflammatory drug aspirin is reported to promote both mitochondrial biogenesis and improvement in cellular energy status.
Methods: Taking altogether the mentioned clues, we evaluated protective effect of aspirin, if any on oligomeric Aβ42 induced toxicity and mitochondrial alterations in differentiated neuronal cells. Results: A significant reduction in neuronal viability and increased apoptosis was observed in Aβ42 treated cells, as evident by MTT assay, apoptosis ELISA and immunofluorescence from β-III tubulin antibody staining of neuronal cells. A concomitant decrease was also observed in the intensity of mitotracker red FM staining and mt-DNA to nDNA ratio, suggesting mitochondrial membrane depolarization and/or reduced number of mitochondria along with depletion in mt-DNA. However, simultaneous treatment of 5 μM aspirin to oligomeric Aβ42 treated cells protected them from mitochondrial dysfunction and neurotoxicity. Conclusion: We suggest mitochondrial biogenesis, changes in mitochondrial membrane potential and / or inhibition of Aβ42 aggregation by aspirin as possible underlying mechanism(s).Export Options
About this article
Cite this article as:
Parmar Singh Hamendra*, Houdek Zbynek, Pesta Martin, Vaclava Cerna, Dvorak Pavel and Hatina Jiri, Protective Effect of Aspirin Against Oligomeric Aβ42 Induced Mitochondrial Alterations and Neurotoxicity in Differentiated EC P19 Neuronal Cells, Current Alzheimer Research 2017; 14 (8) . https://dx.doi.org/10.2174/1567205014666170203104757
DOI https://dx.doi.org/10.2174/1567205014666170203104757 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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