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Differential Transcriptional Alterations In Detoxification Genes In Parkinson’s Disease In Egypt
PD is the most common motor neurodegenerative disease worldwide. The underlying cause of PD is still unknow, owingthis to the complexity of the disease. Often, genetics and environmental factors are collaborating in the initiation of the disease. Despite the diversity of its genetical and environmen...
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2023
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| _version_ | 1867613422995111936 |
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| access_status_str | Open Access |
| author | Shebl, Nourhan |
| author_browse | Shebl, Nourhan |
| author_facet | Shebl, Nourhan |
| author_sort | Shebl, Nourhan |
| collection | Thesis |
| description | PD is the most common motor neurodegenerative disease worldwide. The underlying cause of PD is still unknow, owingthis to the complexity of the disease. Often, genetics and environmental factors are collaborating in the initiation of the disease. Despite the diversity of its genetical and environmental profiles, the Egyptian population is one of the mostunderrepresented population in terms of PD research. In this study, we investigated PD through various perspectives tohighlight the complexity of the disease in Egypt, taking into consideration the diversity of the Egyptian population. We recruited PD patients and reference controls from 4 governorates: Cairo, Giza, Alexandria, and Mansoura to study their genetical and environmental profiles. We collected blood samples and complete clinical, medical, occupational, residential, and family history. Then, we performed several assays such as gene expression, Kompetitive allele specificPCR (KASP) for genotyping, heavy metals assay targeting Al, Cd, Cu, Cr, Mn, Pb, and Ni, and non-target metabolomics. Finally, we statistically correlated and categorized the results in alignment with the clinical data and the completecollected history. Our findings and observations are very promising. We observed that prevalence of the EOPD is higherthan that in other countries. We, also, observed that there is a possible correlation between each of LRRK2 and BCHEK-variant, and pesticides exposure in PD. In our study, we highlighted the complex genetic profile within the Egyptian population in respect to our targeted PD-related genes such as LRRK2, APOE4 and MAPT. Nevertheless, our heavy metals results showed diversity in the distribution among the governorates. On the other hand, and for the first time in PD, we studied the metabolism of phenylalanine via PAL enzyme. This metabolism showed to shift the reaction from producing L-dopa and DA to producing trans cinnamate and ammonia, depriving the neurons from DA and leading to apossible neurotoxicity and, thus, neurodegeneration. Another interesting finding is that we identified a metabolite, 5 Deoxy-5-Methylthioadenosine, that is significantly lower in the K- variant carrier PD patients compared to the non-carrier patients. The reduced levels of the latter metabolite indicate lower glutathione, detoxifying enzyme levels, leaving the K-variant carrier PD patient with higher risk. All these findings and observations showed how complex is the PD profile inthe Egyptian population. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-3216 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:35:54.296Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-3216 Differential Transcriptional Alterations In Detoxification Genes In Parkinson’s Disease In Egypt Shebl, Nourhan PD is the most common motor neurodegenerative disease worldwide. The underlying cause of PD is still unknow, owingthis to the complexity of the disease. Often, genetics and environmental factors are collaborating in the initiation of the disease. Despite the diversity of its genetical and environmental profiles, the Egyptian population is one of the mostunderrepresented population in terms of PD research. In this study, we investigated PD through various perspectives tohighlight the complexity of the disease in Egypt, taking into consideration the diversity of the Egyptian population. We recruited PD patients and reference controls from 4 governorates: Cairo, Giza, Alexandria, and Mansoura to study their genetical and environmental profiles. We collected blood samples and complete clinical, medical, occupational, residential, and family history. Then, we performed several assays such as gene expression, Kompetitive allele specificPCR (KASP) for genotyping, heavy metals assay targeting Al, Cd, Cu, Cr, Mn, Pb, and Ni, and non-target metabolomics. Finally, we statistically correlated and categorized the results in alignment with the clinical data and the completecollected history. Our findings and observations are very promising. We observed that prevalence of the EOPD is higherthan that in other countries. We, also, observed that there is a possible correlation between each of LRRK2 and BCHEK-variant, and pesticides exposure in PD. In our study, we highlighted the complex genetic profile within the Egyptian population in respect to our targeted PD-related genes such as LRRK2, APOE4 and MAPT. Nevertheless, our heavy metals results showed diversity in the distribution among the governorates. On the other hand, and for the first time in PD, we studied the metabolism of phenylalanine via PAL enzyme. This metabolism showed to shift the reaction from producing L-dopa and DA to producing trans cinnamate and ammonia, depriving the neurons from DA and leading to apossible neurotoxicity and, thus, neurodegeneration. Another interesting finding is that we identified a metabolite, 5 Deoxy-5-Methylthioadenosine, that is significantly lower in the K- variant carrier PD patients compared to the non-carrier patients. The reduced levels of the latter metabolite indicate lower glutathione, detoxifying enzyme levels, leaving the K-variant carrier PD patient with higher risk. All these findings and observations showed how complex is the PD profile inthe Egyptian population. 2023-01-31T08:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/2172 https://fount.aucegypt.edu/context/etds/article/3216/viewcontent/Nourhan_Shebl_Thesis.pdf Theses and Dissertations AUC Knowledge Fountain PD Gene-Environment Interaction Metabolomics Phenylalanine K-Variant LRRK2 MAPT APOE Pesticides Exposure Heavy Metals BCHE Biochemical Phenomena, Metabolism, and Nutrition Environmental Public Health Genetic Structures Medical Biochemistry Medical Genetics Medical Molecular Biology Medical Neurobiology Medical Toxicology |
| spellingShingle | PD Gene-Environment Interaction Metabolomics Phenylalanine K-Variant LRRK2 MAPT APOE Pesticides Exposure Heavy Metals BCHE Biochemical Phenomena, Metabolism, and Nutrition Environmental Public Health Genetic Structures Medical Biochemistry Medical Genetics Medical Molecular Biology Medical Neurobiology Medical Toxicology Shebl, Nourhan Differential Transcriptional Alterations In Detoxification Genes In Parkinson’s Disease In Egypt |
| title | Differential Transcriptional Alterations In Detoxification Genes In Parkinson’s Disease In Egypt |
| title_full | Differential Transcriptional Alterations In Detoxification Genes In Parkinson’s Disease In Egypt |
| title_fullStr | Differential Transcriptional Alterations In Detoxification Genes In Parkinson’s Disease In Egypt |
| title_full_unstemmed | Differential Transcriptional Alterations In Detoxification Genes In Parkinson’s Disease In Egypt |
| title_short | Differential Transcriptional Alterations In Detoxification Genes In Parkinson’s Disease In Egypt |
| title_sort | differential transcriptional alterations in detoxification genes in parkinson s disease in egypt |
| topic | PD Gene-Environment Interaction Metabolomics Phenylalanine K-Variant LRRK2 MAPT APOE Pesticides Exposure Heavy Metals BCHE Biochemical Phenomena, Metabolism, and Nutrition Environmental Public Health Genetic Structures Medical Biochemistry Medical Genetics Medical Molecular Biology Medical Neurobiology Medical Toxicology |
| url | https://fount.aucegypt.edu/etds/2172 https://fount.aucegypt.edu/context/etds/article/3216/viewcontent/Nourhan_Shebl_Thesis.pdf |
| work_keys_str_mv | AT sheblnourhan differentialtranscriptionalalterationsindetoxificationgenesinparkinsonsdiseaseinegypt |