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Abstract:   (479 Views)
Introduction: Alzheimer’s disease (AD) is a progressive and chronic neurodegenerative disorder in which amyloid-β (Aβ) and hyperphosphorylated-tau (P-tau) are well-established pathological hallmarks. Carbamylated Erythropoietin (CEPO-Fc) is one of the Erythropoietin derivatives with neuroprotective properties against neurodegenerative disorders. However, the underlying molecular mechanism of CEPO-Fc has not been fully elucidated. Therefore, we investigated the therapeutic effects of CEPO-Fc on Aβ-induced neurotoxicity in the in-vivo rat model.
Methods: Adult male Wistar rats were cannulated in the dorsal hippocampus and Aβ25-35 (5 μg/2.5 μL) was microinjected for four consecutive days. CEPO-Fc (75 or 112 IU) was administered intranasally during the next six consecutive days. Learning and memory performance were examined (days 10-13) using the Morris Water Maze (MWM) test. Furthermore, the hippocampal levels of critical proteins involved in apoptosis (Bax, Bcl-2, and caspase-3), necroptosis [Phosphorylated-Receptor-interacting serine/threonine-protein kinase 3 (p-RIP3)], and autophagy [p-Beclin-1 and phosphorylated- 1A/1B-light chain 3 (p-LC3-II)] were assessed using immunoblotting.
Results: Behavioral analysis showed that CEPO-Fc treatment significantly improved Aβ-induced learning and memory impairment. Furthermore, the hippocampus's molecular analysis showed that CEPO-Fc induced upregulation of the autophagic proteins, p-Beclin-1 and p-LC3-II, while decreased caspase-3, Bax/Bcl2 ratio as well as the necroptosis factor p-RIP3.
Conclusion: Our results indicate that the neuroprotective properties of CEPO-Fc in animal model of AD could be mediated by autophagy activation and inhibition of apoptosis and necroptosis processes. This study introduces CEPO-Fc as a potential protective compound against AD and other neurodegenerative disorders.
     

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