Transcriptome meta-analysis reveals a central role for sex steroids in the degeneration of hippocampal neurons in Alzheimer’s disease

BMC Systems Biology

Howard S Fox¹  Jessica M Winkler¹ 

[1] Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA

关键词: Neurodegeneration;    Hippocampus;    Graph theory;    Estrogen receptor;    Androgen receptor;   

Others  :  1142724
DOI  :  10.1186/1752-0509-7-51

 received in 2012-11-14, accepted in 2013-06-19,  发布年份 2013

【 摘 要 】

Background

Alzheimer’s disease is the most prevalent form of dementia. While a number of transcriptomic studies have been performed on the brains of Alzheimer’s specimens, no clear picture has emerged on the basis of neuronal transcriptional alterations linked to the disease. Therefore we performed a meta-analysis of studies comparing hippocampal neurons in Alzheimer’s disease to controls.

Results

Homeostatic processes, encompassing control of gene expression, apoptosis, and protein synthesis, were identified as disrupted during Alzheimer’s disease. Focusing on the genes carrying out these functions, a protein-protein interaction network was produced for graph theory and cluster exploration. This approach identified the androgen and estrogen receptors as key components and regulators of the disrupted homeostatic processes.

Conclusions

Our systems biology approach was able to identify the importance of the androgen and estrogen receptors in not only homeostatic cellular processes but also the role of other highly central genes in Alzheimer’s neuronal dysfunction. This is important due to the controversies and current work concerning hormone replacement therapy in postmenopausal women, and possibly men, as preventative approaches to ward off this neurodegenerative disorder.

【 授权许可】

   
2013 Winkler and Fox; licensee BioMed Central Ltd.

【 图 表 】

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