PreprintArticleVersion 1This version is not peer-reviewed
Rasagiline Confers Neuroprotection to PC12 Cell Cultures Exposed to Oxygen-Glucose Deprivation/Reoxygenation Insult by Activating the Akt/Nrf2 Redox-Signaling Pathway and by Decreasing the Nuclear Translocation of Glyceraldehyde-3-Phosphate Dehydroge
Version 1
: Received: 27 June 2024 / Approved: 27 June 2024 / Online: 1 July 2024 (08:40:53 CEST)
How to cite:
Lecht, S.; Lahiani, A.; Klazas, M.; Naamneh, M. S.; Rubin, L.; Dong, J.; Zheng, W.; Lazarovici, P. Rasagiline Confers Neuroprotection to PC12 Cell Cultures Exposed to Oxygen-Glucose Deprivation/Reoxygenation Insult by Activating the Akt/Nrf2 Redox-Signaling Pathway and by Decreasing the Nuclear Translocation of Glyceraldehyde-3-Phosphate Dehydroge. Preprints2024, 2024061966. https://doi.org/10.20944/preprints202406.1966.v1
Lecht, S.; Lahiani, A.; Klazas, M.; Naamneh, M. S.; Rubin, L.; Dong, J.; Zheng, W.; Lazarovici, P. Rasagiline Confers Neuroprotection to PC12 Cell Cultures Exposed to Oxygen-Glucose Deprivation/Reoxygenation Insult by Activating the Akt/Nrf2 Redox-Signaling Pathway and by Decreasing the Nuclear Translocation of Glyceraldehyde-3-Phosphate Dehydroge. Preprints 2024, 2024061966. https://doi.org/10.20944/preprints202406.1966.v1
Lecht, S.; Lahiani, A.; Klazas, M.; Naamneh, M. S.; Rubin, L.; Dong, J.; Zheng, W.; Lazarovici, P. Rasagiline Confers Neuroprotection to PC12 Cell Cultures Exposed to Oxygen-Glucose Deprivation/Reoxygenation Insult by Activating the Akt/Nrf2 Redox-Signaling Pathway and by Decreasing the Nuclear Translocation of Glyceraldehyde-3-Phosphate Dehydroge. Preprints2024, 2024061966. https://doi.org/10.20944/preprints202406.1966.v1
APA Style
Lecht, S., Lahiani, A., Klazas, M., Naamneh, M. S., Rubin, L., Dong, J., Zheng, W., & Lazarovici, P. (2024). Rasagiline Confers Neuroprotection to PC12 Cell Cultures Exposed to Oxygen-Glucose Deprivation/Reoxygenation Insult by Activating the Akt/Nrf2 Redox-Signaling Pathway and by Decreasing the Nuclear Translocation of Glyceraldehyde-3-Phosphate Dehydroge. Preprints. https://doi.org/10.20944/preprints202406.1966.v1
Chicago/Turabian Style
Lecht, S., Wenhua Zheng and Philip Lazarovici. 2024 "Rasagiline Confers Neuroprotection to PC12 Cell Cultures Exposed to Oxygen-Glucose Deprivation/Reoxygenation Insult by Activating the Akt/Nrf2 Redox-Signaling Pathway and by Decreasing the Nuclear Translocation of Glyceraldehyde-3-Phosphate Dehydroge" Preprints. https://doi.org/10.20944/preprints202406.1966.v1
Abstract
Rasagiline (Azilect®) is a selective monoamine oxidase B (MAO-B) inhibitor that provides symp-tomatic benefit in Parkinson’s disease (PD) treatment and found to exert preclinical neuroprotec-tive effects. Here, we investigated the neuroprotective signaling pathways of rasagiline in the PC12 neuronal cultures exposed to an ischemic-like insult. Exposure of neurons to oxy-gen-glucose deprivation for 4 h followed by 18 h of reoxygenation caused 40% aponecrotic cell death. Rasagiline induced dose-dependent neuroprotection by decreasing cell death and produc-tion of the neurotoxic reactive oxygen species, and reducing the nuclear translocation of glycer-aldehyde-3-phosphate dehydrogenase (GAPDH). Rasagiline increased protein kinase B (Akt) phosphorylation and decreased protein expression of the ischemia-induced α-synuclein protein, in correlation to the neuroprotective effect. Treatment with rasagiline induced nuclear shuttling of transcription factor Nrf2 and increased the mRNA levels of the antioxidant enzymes heme oxy-genase-1, (NAD (P) H- quinone dehydrogenase, and catalase. These results indicate that rasagiline provides neuroprotection in the ischemic neuronal cultures with inhibition of α-synuclein and GAPDH-mediated aponecrotic cell death, and via mitochondrial protection, as by increasing mi-tochondria-specific antioxidant enzymes by a mechanism involving the Akt/Nrf2 redox-signaling pathway. These findings may be exploited for neuroprotective drug development in PD and stroke therapy.
Medicine and Pharmacology, Neuroscience and Neurology
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