Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.
Undergraduate Student of Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumtani, Thailand.
PeerJ. 2024 Jul 17;12:e17732. doi: 10.7717/peerj.17732. eCollection 2024.
Alzheimer's disease (AD) is a neurodegenerative disease that causes physical damage to neuronal connections, leading to brain atrophy. This disruption of synaptic connections results in mild to severe cognitive impairments. Unfortunately, no effective treatment is currently known to prevent or reverse the symptoms of AD. The aim of this study was to investigate the effects of three synthetic peptides, i.e., KLVFF, RGKLVFFGR and RIIGL, on an AD model represented by differentiated SH-SY5Y neuroblastoma cells exposed to retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). The results demonstrated that RIIGL peptide had the least significant cytotoxic activity to normal SH-SY5Y while exerting high cytotoxicity against the differentiated cells. The mechanism of RIIGL peptide in the differentiated SH-SY5Y was investigated based on changes in secretory proteins compared to another two peptides. A total of 380 proteins were identified, and five of them were significantly detected after treatment with RIIGL peptide. These secretory proteins were found to be related to microtubule-associated protein tau (MAPT) and amyloid-beta precursor protein (APP). RIIGL peptide acts on differentiated SH-SY5Y by regulating amyloid-beta formation, neuron apoptotic process, ceramide catabolic process, and oxidative phosphorylation and thus has the potentials to treat AD.
阿尔茨海默病（AD）是一种神经退行性疾病，会导致神经元连接的物理损伤，从而导致大脑萎缩。这种突触连接的破坏导致轻度至重度认知障碍。不幸的是，目前尚无已知的有效治疗方法可以预防或逆转 AD 的症状。本研究旨在研究三种合成肽，即 KLVFF、RGKLVFFGR 和 RIIGL，对分化的 SH-SY5Y 神经母细胞瘤细胞暴露于维甲酸（RA）和脑源性神经营养因子（BDNF）的 AD 模型的影响。结果表明，RIIGL 肽对正常 SH-SY5Y 的细胞毒性作用最小，但对分化细胞的细胞毒性作用最高。与另外两种肽相比，根据分泌蛋白的变化研究了 RIIGL 肽在分化的 SH-SY5Y 中的作用机制。共鉴定出 380 种蛋白质，其中 5 种在 RIIGL 肽处理后明显检测到。这些分泌蛋白与微管相关蛋白 tau（MAPT）和淀粉样前体蛋白（APP）有关。RIIGL 肽通过调节淀粉样β形成、神经元凋亡过程、神经酰胺分解代谢过程、氧化磷酸化作用于分化的 SH-SY5Y，因此具有治疗 AD 的潜力。
