课题基金 / 基金详情

Role of microRNA-33 in Alzheimer's disease

Role of microRNA-33 in Alzheimer's disease
microRNA-33 在阿尔茨海默病中的作用
批准号:
9338097
负责人:
Jungsu Kim
金额:
$39.35万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-01 至 2021-04-30

项目摘要

项目成果

Jungsu Kim的其他基金

相似基金

相关文献

中文摘要
翻译
点击翻译按钮获取中文摘要
英文摘要
PROJECT SUMMARY/ABSTRACT Mounting evidence suggests that microRNA (miRNA) dysregulation may contribute to psychiatric disorders and neurodegenerative disorders. Although modulations of miRNA function have generated promising clinical data for several diseases, miRNA’s role in Alzheimer’s disease (AD) has not been investigated thoroughly. Apolipoprotein E (ApoE) genotype is the strongest genetic risk factor for AD. In addition to ApoE isoform, alterations in ApoE levels and lipidation status have been shown to influence Aβ aggregation. We and others reported the critical roles of ATP-binding cassette transporter A1 (ABCA1) in regulating ApoE lipidation and Aβ levels in the brain and its therapeutic potential. Increasing evidence suggests that neuroinflammation plays a critical role in AD pathogenesis. Therefore, targeting inflammatory pathways is an emerging therapeutic strategy, along with the direct targeting of ApoE/Aβ pathway, for AD therapy. Recently, we found that miR-33 gene deletion significantly increases ABCA1 levels and soluble Aβ clearance, leading to reduction of soluble Aβ levels in the brain of APP/PS1 mouse model. We also identified that miR-33 regulates neuroinflammation by directly targeting transforming growth factor β (TGFβ) receptor 1 (TGFβR1) gene. Here, we now seek to define the role of miR-33 in ApoE and Amyloid β (Aβ) metabolism in mice (Aim 1) and neuroinflammation (Aim 2). In Aim 1, we will use ABCA1 knockout and ApoE knockout mice along with miR-33 knockout mouse models. In Aim 2, we will use TGFβR1 knockout mouse model. Importantly, we demonstrated that antisense oligonucleotide (ASO)-based pharmacological inhibition of miR-33 efficiently increases ABCA1 levels and reduces soluble Aβ levels in the brain. In Aim 3, we will assess the effect of long-term treatment of anti-miR-33 ASO on Aβ deposition, neuroinflammation, and behavior in mice. We will assess the preventive and therapeutic effect by treating anti-miR-33 ASO before and after the development of Aβ plaques and memory deficits in APP/PS1 mice.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Molecular genetic analyses of transcriptional dysregulation in Alzheimers disease
Molecular genetic analyses of transcriptional dysregulation in Alzheimers disease
The role of ABI3 in Alzheimers disease
The role of ABI3 in Alzheimers disease
海外基金