A systems biology investigation of neurodegenerative dementia reveals a pivotal role of autophagy

BMC Systems Biology

Thanh-Phuong Nguyen¹  Laura Caberlotto¹ 

[1] The Microsoft Research, University of Trento Centre for Computational Systems Biology (COSBI), Piazza Manifattura 1, 38068 Rovereto, Italy

关键词: Amyotrophic lateral sclerosis-Parkinsonism/dementia complex;    Pick’s disease;    Corticobasal dementia;    Progressive supranuclear palsy;    Lewy bodies disease;    Alzheimer’s disease;    Frontotemporal dementia;    AMPK;    GSK-3β;   

Others  :  866350
DOI  :  10.1186/1752-0509-8-65

 received in 2014-01-14, accepted in 2014-05-20,  发布年份 2014

【 摘 要 】

Background

Neurodegenerative dementia comprises chronic and progressive illnesses with major clinical features represented by progressive and permanent loss of cognitive and mental performance, including impairment of memory and brain functions. Many different forms of neurodegenerative dementia exist, but they are all characterized by death of specific subpopulation of neurons and accumulation of proteins in the brain. We incorporated data from OMIM and primary molecular targets of drugs in the different phases of the drug discovery process to try to reveal possible hidden mechanism in neurodegenerative dementia. In the present study, a systems biology approach was used to investigate the molecular connections among seemingly distinct complex diseases with the shared clinical symptoms of dementia that could suggest related disease mechanisms.

Results

Network analysis was applied to characterize an interaction network of disease proteins and drug targets, revealing a major role of metabolism and, predominantly, of autophagy process in dementia and, particularly, in tauopathies. Different phases of the autophagy molecular pathway appear to be implicated in the individual disease pathophysiology and specific drug targets associated to autophagy modulation could be considered for pharmacological intervention. In particular, in view of their centrality and of the direct association to autophagy proteins in the network, PP2A subunits could be suggested as a suitable molecular target for the development of novel drugs.

Conclusion

The present systems biology investigation identifies the autophagy pathway as a central dis-regulated process in neurodegenerative dementia with a prevalent involvement in diseases characterized by tau inclusion and indicates the disease-specific molecules in the pathway that could be considered for therapy.

【 授权许可】

   
2014 Caberlotto and Nguyen; licensee BioMed Central Ltd.

【 图 表 】

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