Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Recently it was shown that nuclear receptor related 1 (Nurr1) play pivotal role in the development and survival of dopaminergic neurons, and its deficiency may be involved in Parkinson{u2019}s disease (PD) pathogenesis. Furthermore, it was revealed that hypoxia-inducible factor-1 alpha (HIF-1Ü) insufficiency and thrombin accumulation are involved in dopaminergic neurons degeneration. Fortunately, Albendazole (ABZ), antihelmintic benzimidazole,was proposed to activate Nurr1 via its benzimidazole group and was shown to promote HIF-1Ü transcription in vitro.Attractively, the new anticoagulant dabigatran etexilate (DE) is a direct thrombin inhibitor that owns benzimidazole group, which has been proposed to activate Nurr1.Therefore, the aim of this study was to explore the neuroprotective effects of ABZ and DE in a rotenone model of PD.Rotenone was injected subcutaneously at a dose of 1.5 mg/kg every other day for 21 days. An oral regimen of ABZ (10 mg/kg) and DE (15 mg/kg) was started after the 5th rotenone injection following the manifestations of PD. Treatment of PD rats with ABZ and DE mitigated rotenone-induced neuronal degeneration and restored striatal dopamine level with motor recovery

Issued also as CD