School of Health Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.
USM-RIKEN Interdisciplinary Centre for Advanced Sciences (URICAS), Universiti Sains Malaysia, 11800, Penang, Malaysia.
Mol Neurobiol. 2023 Aug;60(8):4716-4730. doi: 10.1007/s12035-023-03368-x. Epub 2023 May 5.
Alzheimer's disease (AD) is the most common neurological ailment worldwide. Its process comprises the unique aggregation of extracellular senile plaques composed of amyloid-beta (Aβ) in the brain. Aβ42 is the most neurotoxic and aggressive of the Aβ42 isomers released in the brain. Despite much research on AD, the complete pathophysiology of this disease remains unknown. Technical and ethical constraints place limits on experiments utilizing human subjects. Thus, animal models were used to replicate human diseases. The Drosophila melanogaster is an excellent model for studying both physiological and behavioural aspects of human neurodegenerative illnesses. Here, the negative effects of Aβ42-expression on a Drosophila AD model were investigated through three behavioural assays followed by RNA-seq. The RNA-seq data was verified using qPCR. AD Drosophila expressing human Aβ42 exhibited degenerated eye structures, shortened lifespan, and declined mobility function compared to the wild-type Control. RNA-seq revealed 1496 genes that were differentially expressed from the Aβ42-expressing samples against the control. Among the pathways that were identified from the differentially expressed genes include carbon metabolism, oxidative phosphorylation, antimicrobial peptides, and longevity-regulating pathways. While AD is a complicated neurological condition whose aetiology is influenced by a number of factors, it is hoped that the current data will be sufficient to give a general picture of how Aβ42 influences the disease pathology. The discovery of molecular connections from the current Drosophila AD model offers fresh perspectives on the usage of this Drosophila which could aid in the discovery of new anti-AD medications.
阿尔茨海默病（AD）是全球最常见的神经疾病。其发病过程包括大脑中细胞外老年斑的独特聚集，这些老年斑由淀粉样蛋白-β（Aβ）组成。Aβ42 是大脑中释放的 Aβ42 异构体中最具神经毒性和侵袭性的。尽管对 AD 进行了大量研究，但这种疾病的完整病理生理学仍然未知。技术和伦理限制限制了利用人类受试者进行实验。因此，动物模型被用于复制人类疾病。黑腹果蝇是研究人类神经退行性疾病生理和行为方面的优秀模型。在这里，通过三个行为测定法和 RNA-seq 研究了 Aβ42 表达对果蝇 AD 模型的负面影响。使用 qPCR 验证了 RNA-seq 数据。与野生型对照相比，表达人类 Aβ42 的 AD 果蝇表现出退化的眼部结构、寿命缩短和运动功能下降。RNA-seq 显示，与对照相比，Aβ42 表达样本中有 1496 个基因差异表达。从差异表达基因中鉴定到的途径包括碳代谢、氧化磷酸化、抗菌肽和长寿调节途径。虽然 AD 是一种复杂的神经疾病，其病因受到多种因素的影响，但希望目前的数据足以提供 Aβ42 如何影响疾病病理的大致情况。当前果蝇 AD 模型中分子联系的发现为这种果蝇的使用提供了新的视角，这可能有助于发现新的抗 AD 药物。
