| [1] PubMed ID: | 40375351 |
| Disease Name: | Alzheimer Disease |
| Tissue: | Brain |
| Dysfunction Pattern: | N/A |
| Validated Method: | RT-PCR//Transfection//Luciferase reporter assay//RIP//Western blot//High-throughput sequencing |
| Description: | AD is the most prevalent form of dementia among older adults. Although its etiology is not completely understood, it is generally believed to involve a combination of genetic, environmental, and lifestyle factors [16]. Current diagnostic methods rely on cognitive assessments, neuropsychological tests, neuroimaging techniques (such as magnetic resonance imaging and positron emission tomography), and cerebrospinal fluid analysis [17]. To date, there is no effective cure for AD; Existing treatments only alleviate symptoms and improve quality of life. Therefore, developing and validating novel biomarkers, exploring novel drug targets, and formulating effective therapeutic strategies are critical for early and accurate diagnosis and treatment. Over the years, tsRNAs have garnered significant attention as emerging non-coding RNAs because of their high stability and specificity. TsRNAs play crucial roles in various biological processes, including gene regulation, cellular stress responses, and disease development [9]. Our study is the first to identify that tRFAla-AGC-3-M8 is significantly reduced in case of Aβ deposition in patients with AD. This reduction was negatively correlated with the expression of the target gene EphA7. EphA7 upregulation activates the ERK1/2-p70S6K phosphorylation pathway, which promotes microglial M1-type polarization and enhances tau protein phosphorylation in neurons, leading to neuronal damage. |
| Comparision: | Disease VS Control |
| Mechanism: | TRF and tiRNA from 5’end of tRNAs may be crucial in the pathology of AD. Current evidence suggests that tsRNAs from different sources have distinct biological functions [18], with 5’tRNAs playing vital roles in immunity, hematopoiesis, and intercellular communication [19]. In the context of AD, where neuroinflammation and dysregulated gene expression are hallmark features, the exploration of specific 5’tRNAs may uncover novel regulatory mechanisms underlying disease progression. In our study, we focused on identifying and characterizing 5’tRNAs with potential roles in AD pathogenesis. Through a combination of sequencing analysis and in vivo validation, we identified three key 5’tRNAs tiRNAGly-CCC-2, tRFAla-AGC-3-M8, and tRFGly-TCC-1 as major regulatory molecules. Notably, our statistical results suggest that tRFAla-AGC-3-M8 interacts with EphA7 through an 8mer-1a binding pattern, indicating a perfect match between tRFAla-AGC-3-M8 and nucleotides 2 − 8 in the 3’ UTR of EphA7, with A at position one, suggesting a novel mechanism by which tsRNAs may modulate gene expression in AD. |
|