piRNAs in neurodegenerative diseases: Mechanisms of pathogenesis and therapeutic potential

Introduction: Neurodegenerative disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), and tauopathies are highly prevalent and cause significant public health concerns globally. Although research has focused on pathological proteins such as ?-amyloid, the growing interest in non-coding RNAs, including piRNAs, is shifting the understanding of neurodegenerative disorder mechanisms. Objective: This review aims to summarize the evidence of the role of piRNAs in neurodegenerative disorder pathogenesis and their potential as diagnostic biomarkers. Materials and methods: A systematic review was conducted following PRISMA guidelines. We included randomized controlled trials, cohort studies, and case-control studies focusing on piRNAs in neurodegenerative disorders. Data were extracted from PubMed and ScienceDirect using search terms related to piRNAs and neurodegenerative diseases published between 2009 and 2024. Results: Eleven studies met the inclusion criteria. These studies highlighted the dysregulation of piRNAs in diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, suggesting that piRNAs influence disease mechanisms by maintaining genomic stability, regulating transposable elements, and participating in protein degradation. Several piRNAs, including piR-hsa-92056, emerged as potential biomarkers with diagnostic accuracy. Discussion: The evidence underscores the crucial role of piRNAs in neurodegeneration. Mechanistic studies reveal that piRNA dysfunction may trigger cascades of genomic instability leading to neuronal death. piRNAs are emerging as valuable therapeutic targets and biomarkers in neurodegenerative disorders. Conclusions: piRNAs hold potential as innovative therapeutic and diagnostic tools in NDs. Future research should focus on developing piRNA-based interventions to prevent neurodegeneration.