Research Papers
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Item The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells(Saudi Pharmaceutical Journal, 2023) Ramadan, Azza; Al Mazrouei, Nadia; Mohammed, Abuelnor; Elnour, Asim Ahmed; Sadeq, Adel; Alkaabi, Maisoun; Al-Kubaisi, Khalid Awad; Beshir, Semira Abdi; Menon, Vineetha; AlAmoodi, Abdulla; Sam, Kishore Ganana; Saeed, Ali Awadallah Ali Mohamed; Abdalla, Sami Fatehi; Husse in, Samah MohammedBackground: Huntington’s disease is an inherited progressive neurodegenerative disorder caused by an expansion of the polyglutamine tract leading to malformation and aggregation of the mutant huntingtin protein in the cell cytoplasm and nucleus of affected brain regions. The development of neuroprotective agents from plants has received considerable research attention. Objective: Our study aims to investigate the neuroprotective effects of luteolin and the mechanisms that underline its potential mediated protection in the mutant htt neuroblastoma cells. Methods: The mutant htt neuroblastoma cells were transfected with 160Q, and the control wild-type neuro blastoma cells were transfected with 20Q htt for 24 h and later treated with luteolin. Cell viability was deter mined by MTT and PI staining in both groups, while western blotting was used to evaluate caspase 3 protein expression. Aggregation formation was assessed via immunofluorescence microscopy. Also, western blotting was utilized to measure the protein expression of mutant htt aggregated and soluble protein, Nrf2 and HO-1. The impact of Nrf2 on luteolin-treated neuroblastoma cells was assessed using small interfering RNAs. Results: Our study reports that luteolin can protect cultured cells from mutant huntingtin cytotoxicity, evidenced by increased viability and decreased apoptosis. Also, luteolin reduced the accumulation of soluble and insoluble mutant huntingtin aggregates in mutant htt neuroblastoma cells transfected with 160Q compared to the control wild-type. The mutant htt aggregate reduction mediated by luteolin appeared to be independent of the Nrf2 –HO- 1 antioxidant pathway. Conclusion: Luteolin presents a new potential therapeutic and protective agent for the treatment and decreasing the cytotoxicity in neurodegenerative diseases such as Huntington’s disease.Item Luteolin as potential treatment for Huntington's disease: Insights from a transgenic mouse model(CNS Neuroscience & Therapeutics, 2024) Mohammed, Abuelnor; Ramadan, Azza; Elnour, Asim Ahmed; Saeed, Ali Awadallah Ali Mohamed; Al Mazrouei, Nadia; Alsulami, Fahad T.; Alqarni, Yousef Saeed; Menon, Vineetha; Al Amoodi, Abdulla; Abdalla, Sami FatehiAims: The study aimed to evaluate the potential benefits of luteolin treatment in Huntington's disease (HD), an inherited progressive neurodegenerative disorder. Methods: HD N171- 82Q transgenic and WT mice received luteolin or vehicle for treat ment at 6 weeks of age. The mice's body weight changes and survival rates were moni tored throughout the study, and a series of motor functional tests were conducted. Serum level of the marker NfL was also determined. Immunohistochemical staining and western blotting were utilized to assess the expression of huntingtin aggregates. Results: Luteolin treatment enhanced survival and prevented weight loss in HD mice compared to the vehicle- treated HD group. Furthermore, the luteolin- treated HD mice exhibited enhanced motor coordination and balance and significantly reduced motor dysfunction. Also, luteolin decreased serum NfL levels in HD mice. Notably, the accumulation of huntingtin aggregates was significantly reduced in the brain's cortex, hippocampus, and striatum of luteolin- treated HD mice compared to the vehicle- treated HD group. Conclusion: Luteolin holds promise as a therapeutic agent for improving survival out comes, managing motor dysfunction, and reducing huntingtin aggregates in HD. The findings are of significance as currently, there are no approved therapeutic interven tions that reverse HD pathology or slow down its progression.