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Uncovering the Regulatory Role of miRNAs in Parkinson’s Disease: A Case Study of an Egyptian Family with a Novel Mutation
The study investigates how the mitochondrial peptidase PITRM1 mutation reshapes the miRNA landscape and contributes to the development of Parkinson’s disease (PD). It also examines how these alterations intersect with the molecular pathways implicated in Alzheimer’s disease (AD), highlighting the me...
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| Format: | Thesis |
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AUC Knowledge Fountain
2026
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| _version_ | 1867613433499746304 |
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| access_status_str | Open Access |
| author | Abdoun, Rana Reda |
| author_browse | Abdoun, Rana Reda |
| author_facet | Abdoun, Rana Reda |
| author_sort | Abdoun, Rana Reda |
| collection | Thesis |
| description | The study investigates how the mitochondrial peptidase PITRM1 mutation reshapes the miRNA landscape and contributes to the development of Parkinson’s disease (PD). It also examines how these alterations intersect with the molecular pathways implicated in Alzheimer’s disease (AD), highlighting the mediated cross-talk between the two diseases. Leveraging the small RNA sequencing from healthy controls, asymptomatic PITRM1 R892K carriers, and PITRM1 associated PD patients identified in an Egyptian family, the study reveals a compact but highly dysregulated miRNAs panel that segregates mutation carriers from the clinical disease. In PD vs carriers, miR‑141‑5p, miR‑205‑5p, miR‑138‑5p, miR‑885‑3p, miR‑196a‑5p, miR‑3140‑3p, and miR‑1238‑3p are strongly upregulated, whereas miR‑4422, miR‑496, and miR‑4435 are markedly downregulated. The KEGG pathway and gene ontology enrichment analysis pinpoint that the predicted and validated targets of these miRNAs are predominantly enriched in protein targeting to mitochondria, PI3K/AKT- mTOR and MAPK signaling, oxidative stress response, autophagy lysosomal flux, and broader proteostasis networks. Asymptomatic carriers display a modest and often opposite changes in specific miRNAs including; miR‑3140‑3p and miR‑1238‑3p, supporting the biphasic mechanism in which early miRNA adaptations help buffer PITRM1-dependent mitochondrial stress which eventually becomes maladaptive as damage accumulates. Integrating these findings with the current experimental literature positioned PITRM1 as the upstream driver of mitochondrial proteotoxicity and Aβ handling. PITRM1 indirectly sculpts the disease- defining miRNA network rather than being directly targeted by it. This precise association mechanistically links PD and AD at the level of mitostasis and proteostasis. Overall, the works reveals a PITRM1-related miRNA signature with potential utility as a circulating biomarker panel that stratify carriers at the risk of developing PD symptoms. It also serves as a conceptual framework miRNA guided intervention, aiming at restoring mitochondrial quality control and rebalance PI3K/AKT-mTOR and stress response pathways in PITRM1 associated and sporadic PD. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-3796 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:36:04.472Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-3796 Uncovering the Regulatory Role of miRNAs in Parkinson’s Disease: A Case Study of an Egyptian Family with a Novel Mutation Abdoun, Rana Reda The study investigates how the mitochondrial peptidase PITRM1 mutation reshapes the miRNA landscape and contributes to the development of Parkinson’s disease (PD). It also examines how these alterations intersect with the molecular pathways implicated in Alzheimer’s disease (AD), highlighting the mediated cross-talk between the two diseases. Leveraging the small RNA sequencing from healthy controls, asymptomatic PITRM1 R892K carriers, and PITRM1 associated PD patients identified in an Egyptian family, the study reveals a compact but highly dysregulated miRNAs panel that segregates mutation carriers from the clinical disease. In PD vs carriers, miR‑141‑5p, miR‑205‑5p, miR‑138‑5p, miR‑885‑3p, miR‑196a‑5p, miR‑3140‑3p, and miR‑1238‑3p are strongly upregulated, whereas miR‑4422, miR‑496, and miR‑4435 are markedly downregulated. The KEGG pathway and gene ontology enrichment analysis pinpoint that the predicted and validated targets of these miRNAs are predominantly enriched in protein targeting to mitochondria, PI3K/AKT- mTOR and MAPK signaling, oxidative stress response, autophagy lysosomal flux, and broader proteostasis networks. Asymptomatic carriers display a modest and often opposite changes in specific miRNAs including; miR‑3140‑3p and miR‑1238‑3p, supporting the biphasic mechanism in which early miRNA adaptations help buffer PITRM1-dependent mitochondrial stress which eventually becomes maladaptive as damage accumulates. Integrating these findings with the current experimental literature positioned PITRM1 as the upstream driver of mitochondrial proteotoxicity and Aβ handling. PITRM1 indirectly sculpts the disease- defining miRNA network rather than being directly targeted by it. This precise association mechanistically links PD and AD at the level of mitostasis and proteostasis. Overall, the works reveals a PITRM1-related miRNA signature with potential utility as a circulating biomarker panel that stratify carriers at the risk of developing PD symptoms. It also serves as a conceptual framework miRNA guided intervention, aiming at restoring mitochondrial quality control and rebalance PI3K/AKT-mTOR and stress response pathways in PITRM1 associated and sporadic PD. 2026-06-15T07:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/2737 https://fount.aucegypt.edu/context/etds/article/3796/viewcontent/Final_Thesis__Rana_Abdoun.pdf Theses and Dissertations AUC Knowledge Fountain PITRM1 Parkinson's Disease miRNA sequencing Alzheimer's Disease Mitochondrial Quality Control Neuroscience and Neurobiology |
| spellingShingle | PITRM1 Parkinson's Disease miRNA sequencing Alzheimer's Disease Mitochondrial Quality Control Neuroscience and Neurobiology Abdoun, Rana Reda Uncovering the Regulatory Role of miRNAs in Parkinson’s Disease: A Case Study of an Egyptian Family with a Novel Mutation |
| title | Uncovering the Regulatory Role of miRNAs in Parkinson’s Disease: A Case Study of an Egyptian Family with a Novel Mutation |
| title_full | Uncovering the Regulatory Role of miRNAs in Parkinson’s Disease: A Case Study of an Egyptian Family with a Novel Mutation |
| title_fullStr | Uncovering the Regulatory Role of miRNAs in Parkinson’s Disease: A Case Study of an Egyptian Family with a Novel Mutation |
| title_full_unstemmed | Uncovering the Regulatory Role of miRNAs in Parkinson’s Disease: A Case Study of an Egyptian Family with a Novel Mutation |
| title_short | Uncovering the Regulatory Role of miRNAs in Parkinson’s Disease: A Case Study of an Egyptian Family with a Novel Mutation |
| title_sort | uncovering the regulatory role of mirnas in parkinson s disease a case study of an egyptian family with a novel mutation |
| topic | PITRM1 Parkinson's Disease miRNA sequencing Alzheimer's Disease Mitochondrial Quality Control Neuroscience and Neurobiology |
| url | https://fount.aucegypt.edu/etds/2737 https://fount.aucegypt.edu/context/etds/article/3796/viewcontent/Final_Thesis__Rana_Abdoun.pdf |
| work_keys_str_mv | AT abdounranareda uncoveringtheregulatoryroleofmirnasinparkinsonsdiseaseacasestudyofanegyptianfamilywithanovelmutation |