The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells
Background: 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 neur...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Saudi Pharmaceutical Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016423003663 |
| _version_ | 1797390549189132288 |
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| author | Azza Ramadan Abuelnor Mohammed Asim Ahmed Elnour Adel Sadeq Nadia Al Mazrouei Maisoun Alkaabi Khalid Awad Al-Kubaisi Semira Abdi Beshir Vineetha Menon Abdulla AlAmoodi Kishore Ganana Sam Ali Awadallah Ali Mohamed Saeed Sami Fatehi Abdalla Samah Mohammed Hussein |
| author_facet | Azza Ramadan Abuelnor Mohammed Asim Ahmed Elnour Adel Sadeq Nadia Al Mazrouei Maisoun Alkaabi Khalid Awad Al-Kubaisi Semira Abdi Beshir Vineetha Menon Abdulla AlAmoodi Kishore Ganana Sam Ali Awadallah Ali Mohamed Saeed Sami Fatehi Abdalla Samah Mohammed Hussein |
| author_sort | Azza Ramadan |
| collection | DOAJ |
| description | Background: 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 neuroblastoma cells were transfected with 20Q htt for 24 h and later treated with luteolin. Cell viability was determined 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. |
| first_indexed | 2024-03-08T23:13:25Z |
| format | Article |
| id | doaj.art-618baeb1e0c146daae851bdfa9325550 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-03-08T23:13:25Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-618baeb1e0c146daae851bdfa93255502023-12-15T07:23:00ZengElsevierSaudi Pharmaceutical Journal1319-01642023-12-013112101871The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cellsAzza Ramadan0Abuelnor Mohammed1Asim Ahmed Elnour2Adel Sadeq3Nadia Al Mazrouei4Maisoun Alkaabi5Khalid Awad Al-Kubaisi6Semira Abdi Beshir7Vineetha Menon8Abdulla AlAmoodi9Kishore Ganana Sam10Ali Awadallah Ali Mohamed Saeed11Sami Fatehi Abdalla12Samah Mohammed Hussein13College of Pharmacy, Al Ain University, Abu Dhabi Campus Abu Dhabi, UAE, AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, United Arab EmiratesDepartment of Basic Medical Sciences, College of Medical, Dar Al Uloom University, Riyadh, Saudi Arabia; Department of Histology and Embryology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, People’s Republic of China; Corresponding author at: Department of Basic Medical Sciences, College of Medical, Dar Al Uloom University, Riyadh, Saudi Arabia.Program of Clinical Pharmacy, College of Pharmacy, Al Ain University, Abu Dhabi campus, Abu Dhabi-United Arab Emirates (UAE), AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, United Arab EmiratesProgram of Clinical Pharmacy, College of Pharmacy, Al Ain University, Al Ain, United Arab EmiratesDepartment of Pharmacy Practice and Pharmacotherapeutics, Faculty of Pharmacy, University of Sharjah, United Arab EmiratesNew Medical Center (NMC) Royal Women’s Hospital, Abu Dhabi, United Arab EmiratesDepartment of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy-University of Sharjah, United Arab EmiratesDepartment of Clinical Pharmacy and Pharmacotherapeutics, Dubai Pharmacy College For Girls, Dubai, United Arab EmiratesDepartment of Pharmacy Practice, College of Pharmacy, Gulf Medical University, United Arab EmiratesAmbulatory Healthcare Services, Academic Affairs, Abu Dhabi Health Services (SEHA), United Arab EmiratesDepartment of Clinical Pharmacy and Pharmacotherapeutics, Dubai, United Arab EmiratesDepartment of Pharmacology, Faculty of Clinical and Industrial Pharmacy, National University-Sudan, Mycetoma Research Center, Khartoum, SudanClinical Department, College of Medicine, University of Almaarefa, Riyadh, Saudi ArabiaDepartment of Pharmacy Practice, Unaizah College of Pharmacy, Qassim University, Buraydah 52571, Saudi ArabiaBackground: 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 neuroblastoma cells were transfected with 20Q htt for 24 h and later treated with luteolin. Cell viability was determined 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.http://www.sciencedirect.com/science/article/pii/S1319016423003663AggregationHuntington’s diseaseLuteolin, misfolded proteinNeurodegenerative diseases |
| spellingShingle | Azza Ramadan Abuelnor Mohammed Asim Ahmed Elnour Adel Sadeq Nadia Al Mazrouei Maisoun Alkaabi Khalid Awad Al-Kubaisi Semira Abdi Beshir Vineetha Menon Abdulla AlAmoodi Kishore Ganana Sam Ali Awadallah Ali Mohamed Saeed Sami Fatehi Abdalla Samah Mohammed Hussein The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells Saudi Pharmaceutical Journal Aggregation Huntington’s disease Luteolin, misfolded protein Neurodegenerative diseases |
| title | The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells |
| title_full | The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells |
| title_fullStr | The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells |
| title_full_unstemmed | The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells |
| title_short | The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells |
| title_sort | flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin mutated neuroblastoma cells |
| topic | Aggregation Huntington’s disease Luteolin, misfolded protein Neurodegenerative diseases |
| url | http://www.sciencedirect.com/science/article/pii/S1319016423003663 |
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