Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene.

Judith A Potashkin,Virginie Bottero,James P Quinn,Jose A Santiago

doi:10.3390/ijms21113787

Abstract

The mechanisms that initiate dementia are poorly understood and there are currently no treatments that can slow their progression. The identification of key genes and molecular pathways that may trigger dementia should help reveal potential therapeutic reagents. In this study, SWItch Miner software was used to identify phosphodiesterase 4D-interacting protein as a key factor that may lead to the development of Alzheimer’s disease, vascular dementia, and frontotemporal dementia. Inflammation, PI3K-AKT, and ubiquitin-mediated proteolysis were identified as the main pathways that are dysregulated in these dementias. All of these dementias are regulated by 12 shared transcription factors. Protein–chemical interaction network analysis of dementia switch genes revealed that valproic acid may be neuroprotective for these dementias. Collectively, we identified shared and unique dysregulated gene expression, pathways and regulatory factors among dementias. New key mechanisms that lead to the development of dementia were revealed and it is expected that these data will advance personalized medicine for patients.

Highlights

Dementia is a syndrome that often manifests itself as a reduction in cognitive function, especially with regards to memory and thinking [1]
We found that phosphodiesterase 4D interacting protein (PDE4DIP) was the only switch gene shared among the three groups (Figure 5)
The results presented in this study support the fact that Alzheimer’s disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD) may develop from the dysregulation of several pathways that are not shared among all three dementias

Summary

Introduction

Dementia is a syndrome that often manifests itself as a reduction in cognitive function, especially with regards to memory and thinking [1]. Social behavioral changes, and motivation tend to decline in dementia patients [1]. Dementia is often a major cause of chronic disability and dependency among the elderly. According to the World Health Organization, approximately 50 million people have dementia and 20% of those are newly diagnosed patients [1]. The different dementias share several genetic, neurochemical, and morphological factors, making their distinction very challenging [2,3]. Compounding this problem is the fact that mixed forms of dementia are often present in a patient [2]. There are currently no known means of preventing dementia and no treatments that slow progression or cure the disorder [1]

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Discussion

Conclusion