Abstract
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.
School
School of Sciences and Engineering
Department
Biotechnology Program
Degree Name
MS in Biotechnology
Graduation Date
Summer 6-15-2026
Submission Date
2-11-2026
First Advisor
Maya Nicolas
Committee Member 1
Mohamed Salama
Committee Member 2
Raghda Ramadan
Committee Member 3
Anwar Abdelnaser
Extent
97 p.
Document Type
Master's Thesis
Institutional Review Board (IRB) Approval
Approval has been obtained for this item
Disclosure of AI Use
Thesis editing and/or reviewing; Code/algorithm generation and/or validation
Recommended Citation
APA Citation
Abdoun, R. R.
(2026).Uncovering the Regulatory Role of miRNAs in Parkinson’s Disease: A Case Study of an Egyptian Family with a Novel Mutation [Master's Thesis, the American University in Cairo]. AUC Knowledge Fountain.
https://fount.aucegypt.edu/etds/2737
MLA Citation
Abdoun, Rana Reda. Uncovering the Regulatory Role of miRNAs in Parkinson’s Disease: A Case Study of an Egyptian Family with a Novel Mutation. 2026. American University in Cairo, Master's Thesis. AUC Knowledge Fountain.
https://fount.aucegypt.edu/etds/2737