Hamendra Singh Parmar*, Zbynek Houdek, Martin Pesta, Cerna Vaclava, Pavel Dvorak and Jiri Hatina Pages 810 - 819 ( 10 )
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. <p></p> 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. <p></p> 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. <p></p> Conclusion: We suggest mitochondrial biogenesis, changes in mitochondrial membrane potential and / or inhibition of Aβ42 aggregation by aspirin as possible underlying mechanism(s). <p></p>
Aspirin, oligomeric-Aβ42, EC P19 cells, mitochondrial dysfunction, neurotoxicity, mt-DNA/nDNA.
School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore- 452001, M.P., Department of Biology, Faculty of Medicine in Pilsen, Charles University- in Prague, Alej Svobody 1655/76, 32300, Pilsen, Department of Biology, Faculty of Medicine in Pilsen, Charles University- in Prague, Alej Svobody 1655/76, 32300, Pilsen, Department of Biology, Faculty of Medicine in Pilsen, Charles University- in Prague, Alej Svobody 1655/76, 32300, Pilsen, Department of Biology, Faculty of Medicine in Pilsen, Charles University- in Prague, Alej Svobody 1655/76, 32300, Pilsen, Department of Biology, Faculty of Medicine in Pilsen, Charles University- in Prague, Alej Svobody 1655/76, 32300, Pilsen