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Physiology and Pharmacology، جلد ۲۶، شماره ۳، صفحات ۲۷۲-۲۸۷

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عنوان انگلیسی Carbamylated erythropoietin-Fc ameliorates Aβ25-35 induced neurotoxicity by modulating autophagy, apoptosis and necroptosis in Alzheimer’s disease model rats
چکیده انگلیسی مقاله 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 was microinjected for four consecutive days. CEPO-Fc was administered intranasally during the next six consecutive days. Learning and memory performance were examined (days 10-13) using the Morris water maze test. Furthermore, the hippocampal levels of critical proteins involved in apoptosis (Bax, Bcl-2 and caspase-3), necroptosis (phosphorylatedreceptor-interacting serine/threonine-protein kinase 3) and autophagy (p-Beclinbeclin-1 and phosphorylated- 1A/1B-light chain 3) 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 up-regulation 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.
کلیدواژه‌های انگلیسی مقاله Alzheimer&apos,s disease, CEPO-Fc, Apoptosis, Autophagy, Necroptosis

نویسندگان مقاله | Amirhossein Maghsoudi
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran


| Jalal Zaringhalam
Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran


| Maryam Moosavi
Nanomedicine and Nanobiology Research Centre, Shiraz University of Medical sciences, Shiraz, Iran


| Akram Eidi
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran



نشانی اینترنتی http://ppj.phypha.ir/browse.php?a_code=A-10-1604-1&slc_lang=en&sid=1
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زبان مقاله منتشر شده en
موضوعات مقاله منتشر شده Neurophysiology/Pharmacology
نوع مقاله منتشر شده Experimental research article
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