脑部微环境与microrna-107的关系及化合物hx24促突起生长作用分析-relationship between brain microenvironment and microrna - 107 and analysis of compound hx24 promoting neurite growth.docxVIP

AB ABSTRACT IV IV ABSTRACT Part 1 The Impact of Cerebral Microenviroment on MiR-107 Alzheimers disease (AD) is a neurodegenerative disease and the most common form of dementia among the elderly. After heart disease, cancer and stroke, Alzheimers disease has become the fourth largest cause of death on elderly. Although the pathogenesis of AD is not very clear, it’s accepted that Aβ aggregation deposition plays a key role in the pathogenesis of AD. Aβ is derived from the amyloid precursor protein catalysed by the β-secretase (BACE1) and γ-secretase. BACE1 is the rate-limiting enzyme in this biological processes. MicroRNA(~22nt) are non-coding single strand RNA molecules, and is a member of genes regulating family found in the evolution of plants and animals. In our clinical study, we find that miR-107 in the MCI and AD patients was significantly lower than normal control. In addition, there have been reported that BACE1 is a target gene of miR-107. Prompting us that miR-107 reduction in patients is closely related to BACE1 increase and Aβ generation. It is noteworthy that, age is the most direct sick standards of Alzheimers disease, and the ability of the elderly to regulate the change of brain microenvironment is decline. We simulate the pathological conditions of microenvironment at the cellular level, including the mild endoplasmic reticulum stress, mild oxidative stress, inflammatory environment, hypoxia, glucose deprivation. Using Western blot and found endoplasmic reticulum stress and inflammatory environment can significantly increase the expression of BACE1 protein. Using real-time quantitative PCR, the mRNA level get consistent results with protein levels. We want to know whether miR-107 will play a role in this process. We so detect the expression levels of miR-107, and find miR-107 have not changed in the endoplasmic reticulum stress and mild inflammatory environment. In the endoplasmic reticulum stress, cell is transfected with miR-107 mimics and inhibitor