Articles

Early-onset neurodegenerative diseases (EO-NDs), such as early-onset Alzheimer’s disease (EOAD), Parkinson’s disease (EOPD), and familial amyotrophic lateral sclerosis (fALS), often stem from monogenic causes and manifest before typical age thresholds. These disorders frequently feature disrupted mitochondrial function and heightened oxidative stress, which together accelerate neuronal damage and degeneration. In this work, the author performs a comprehensive analysis of the literature and data related to mitochondrial dysfunction and redox imbalance in EO-NDs. Bibliometric trends were assessed using R-based tools on PubMed datasets, highlighting keyword networks and publication surges in recent years. Publicly available RNA-seq datasets from GEO and SRA were examined, with example DESeq2 analysis illustrating altered mitochondrial gene expression in EO-ND patient-derived samples. Network modeling of redox pathways using Python’s networkx demonstrates how oxidative stress can propagate through metabolic networks. Together, these computational approaches reinforce that mitochondrial DNA mutations, impaired electron transport chain (ETC) function, and reactive oxygen species (ROS) accumulation play central roles in EO-ND pathogenesis. The discussion further evaluates why antioxidant clinical trials have largely failed and how emerging therapies such as gene replacement, antisense oligonucleotides, and mitochondrial biogenesis modulators may provide more effective interventions.