PDF(Pubmed)
Abstract：
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 in vitro 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.
摘要：
阿尔茨海默病（AD）是一种神经退行性疾病，会对神经元连接造成物理损伤，导致脑萎缩.突触连接的这种破坏导致轻度到重度的认知损害。不幸的是,目前已知没有有效的治疗方法可以预防或逆转AD的症状。这项研究的目的是研究三种合成肽的作用，即，KLVFF,RGKLVFFGR和RIIGL,以暴露于视黄酸（RA）和脑源性神经营养因子（BDNF）的分化SH-SY5Y神经母细胞瘤细胞为代表的AD体外模型。结果表明，RIIGL肽对正常SH-SY5Y具有最小的细胞毒活性，同时对分化细胞具有较高的细胞毒性。基于与另外两种肽相比分泌蛋白的变化，研究了RIIGL肽在分化的SH-SY5Y中的机制。共鉴定出380种蛋白质,用RIIGL肽治疗后，其中5例检测到。发现这些分泌蛋白与微管相关蛋白tau（MAPT）和淀粉样β前体蛋白（APP）有关。RIIGL肽通过调节β淀粉样蛋白的形成作用于分化的SH-SY5Y，神经元凋亡过程，神经酰胺分解代谢过程，和氧化磷酸化，因此具有治疗AD的潜力。
