Nahalka Jozef
Institute of Chemistry, Centre for Glycomics, Slovak Academy of Sciences, Dubravska Cesta 9, SK-84538 Bratislava, Slovakia.
Institute of Chemistry, Centre of Excellence for White-Green Biotechnology, Slovak Academy of Sciences, Trieda Andreja Hlinku 2, SK-94976 Nitra, Slovakia.
Curr Issues Mol Biol. 2022 Aug 9;44(8):3533-3551. doi: 10.3390/cimb44080243.
Alzheimer's disease is a very complex disease and better explanations and models are needed to understand how neurons are affected and microglia are activated. A new model of Alzheimer's disease is presented here, the β-amyloid peptide is considered an important RNA recognition/binding peptide. 1-L transcription revealed compatible sequences with AAUAAA (PAS signal) and UUUC (class III ARE rich in U) in the Aβ peptide, supporting the peptide-RNA regulatory model. When a hypothetical model of fibril selection with the prionic character of amyloid assemblies is added to the peptide-RNA regulatory model, the downregulation of the PI3K-Akt pathway and the upregulation of the PLC-IP3 pathway are well explained. The model explains why neurons are less protected from inflammation and why microglia are activated; why mitochondria are destabilized; why the autophagic flux is destabilized; and why the post-transcriptional attenuation of the axonal signal "noise" is interrupted. For example, the model suggests that Aβ peptide may post-transcriptionally control ELAVL2 (ELAV-like RNA binding protein 2) and DCP2 (decapping mRNA protein 2), which are known to regulate RNA processing, transport, and stability.
阿尔茨海默病是一种非常复杂的疾病，需要更好的解释和模型来理解神经元是如何受到影响以及小胶质细胞是如何被激活的。本文提出了一种新的阿尔茨海默病模型，β-淀粉样肽被认为是一种重要的RNA识别/结合肽。1-L转录揭示了Aβ肽中与AAUAAA（多聚腺苷酸化信号）和UUUC（富含U的III类富含AU元件）兼容的序列，支持了肽-RNA调控模型。当将具有淀粉样蛋白聚集体朊病毒特性的原纤维选择假设模型添加到肽-RNA调控模型中时，PI3K-Akt途径的下调和PLC-IP3途径的上调就得到了很好的解释。该模型解释了为什么神经元对炎症的保护作用较弱以及为什么小胶质细胞会被激活；为什么线粒体不稳定；为什么自噬通量不稳定；以及为什么轴突信号“噪声”的转录后衰减会被中断。例如，该模型表明Aβ肽可能在转录后控制ELAVL2（ELAV样RNA结合蛋白2）和DCP2（去帽mRNA蛋白2），已知它们可调节RNA加工、运输和稳定性。
