| Alzheimer's disease?AD? is a kind of irreversible and progressive neurodegenerative disorder and becomes a major healthy issue in the world. There are approximate 36 million AD patients in the world, and it becomes the sixth leading cause of death in the UK over 65 year older, and the fifth leading cause of death in the United States. In India, it is reported that 3.7 million people over 60 years suffer from AD. With the rapid economic development and social progress, China is entering an aging society gradually with the increase of elderly population. There are more than 5 million patients who suffer from AD in China. The mortality of AD is very high, only following cardiovascular disease, cerebrovascular disease and cancer. Therefore, it has seriously affected people's health and the quality of life, bringing a huge pressure on social and family. As a result, its prevention and treatment become a focus of medicine. There is a variety of theories about the pathogenesis of AD, including amyloid cascade hypothesis, insulin hypothesis, defective axonal transport hypothesis, cholinergic hypothesis and tau phosphorylation hypothesis, but the amyloid cascade hypothesis is accepted universally, which indicates that A?'s neurotoxicity to neocortex and hippocampus. According to the theory, A? protein may trigger a series of pathological cascade reactions in brain, including the intracellular calcium ion concentration, inflammation, axon and synaptic damage, neurofibrillary tangles. Finally, they cause neural dysfunction and cell death. Studies have confirmed that A? can play neurotoxic roles through a variety of mechanisms, however, A? neurotoxicity to cytoskeleton is not understood well, especially the relationship between the disintegration of cytoskeleton and the pathogenesis of AD.Cytoskeleton is fiber network system in eukaryotic cells, mainly consisting of three different structures, namely microtubules, microfilament and intermediate filaments. Recent studies have showed that the changes of cytoskeleton are very active in the process of cell apoptosis, since they even can regulate apoptotic signals directly. As we know that cytoskeleton plays an important role to maintain the structure and function of neurons, therefore dysfunction of cytoskeleton results in the occurrence and development of a variety of neurodegenerative diseases. Moreover, the abnormalities of neuronal microtubules are considered the main cause AD. In present study, PC12 cells were used as neuronal model, and A?25-35 was treated to PC12 cells as neurotoxicity. Therefore, the cell apoptosis and alterations of cytoskeleton and were investigated. No doubt, the present study will be helpful for us to reveal the cause and pathogenesis of AD. Hopefully, the cytoskeleton probably becomes a potential drug target for AD therapy.Aims: We tried to establish the cell model of Alzheimer's disease?AD? and investigate the A?25-35 neurotoxicity to cells' cytoskeleton as well.Methods: PC12 cells were cultured and treated with A?25-35, and cell survival was analyzed by MTT assay. In the meantime, cell apoptosis was visualized with DAPI staining and TUNEL method. Immunocytochemistry and phalloidin staining were used to label cytoskeletons in PC12 cells.Results: A?25-35 could obviously induce the PC12 cells death and apoptosis with dose dependency?P < 0.05?. A?25-35 could also cause the disintegration of cytoskeletons with dose dependency as well?P < 0.05?.Conclusion: PC12 cells' cytoskeletons are sensitive to A?25-35 neurotoxicity. A?25-35 could induce the disintegration of the cytoskeleton. The disintegration of cytoskeleton probably is the important pathological alterations in AD, and A? is a key molecule for AD pathogenesis. |
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