El-Seedy Ayman, Ladevèze Véronique
Laboratory of Cellular and Molecular Genetics, Department of Genetics, Alexandria University, Aflaton Street, El-Shatby, Alexandria 21545, Egypt.
Laboratoire MOVE-UR20296, University of Poitiers, Pôle Biologie Santé-Bât B36, 1 rue G. Bonnet-TSA 51156, Cedex 9, 86073 Poitiers, France.
Genes (Basel). 2025 Jun 30;16(7):782. doi: 10.3390/genes16070782.
Determining the genetic variations of candidate genes in affected subjects will help identify early pathological biomarkers of Alzheimer's disease (AD) and develop effective treatments. It has recently been found that some genes that are linked share an increase in intron retention (IR). In this review, we discuss a few instances of mRNA-IR in various genes linked to AD, including , , , , , , , , and genes. These genes are vulnerable to IR, encompassing additional crucial proteins for brain functionality, but they are frequently involved in pathways linked to the control of mRNA and protein homeostasis. Despite the advancements in human in vivo RNA therapy, as far as we know, there are no reports of data generated regarding artificial in vivo splicing in either animal models or humans. To prevent genetic variations and improve or repair errors in expression of desired genes, humans have adopted new gene editing techniques like CRISPR-Cas9 and RNAi modalities. Ultimately, IR could be utilized as a therapeutic potential biomarker for disorders related to intronic expansion.
确定受影响个体中候选基因的遗传变异将有助于识别阿尔茨海默病（AD）的早期病理生物标志物并开发有效的治疗方法。最近发现，一些相关基因的内含子保留（IR）有所增加。在本综述中，我们讨论了与AD相关的各种基因中的一些mRNA-IR实例，包括 、 、 、 、 、 、 、 和 基因。这些基因易受IR影响，包含对大脑功能至关重要的其他蛋白质，但它们经常参与与mRNA和蛋白质稳态控制相关的途径。尽管人类体内RNA治疗取得了进展，但据我们所知，在动物模型或人类中均没有关于人工体内剪接产生的数据报告。为了防止遗传变异并改善或修复所需基因表达中的错误，人类采用了新的基因编辑技术，如CRISPR-Cas9和RNAi方法。最终，IR可作为与内含子扩增相关疾病的治疗潜在生物标志物。
