poster The central role of AMP-kinase and energy homeostasis impairment in Alzheimer’s disease: a multifactor network analysis.


Abstract

The emerging tools of network analysis in medicine offer a platform to explore systematically the molecular complexity of multifactorial disease identifying previously unidentified disease relevant genes based on analysis of the protein-protein interaction network. To unravel the molecular basis of Alzheimer’s disease, convergent analysis of multi-dimensional datasets was performed providing a systematic view of the evidence in the genomic, transcriptomic, and in the molecular targets of drugs. We have used data available from multiple sources to characterize enriched modules in the context of a protein-protein interaction network. Functional enrichment analyses of Gene Ontology (GO) terms of the modules was then performed evidencing a prevalent enrichment in terms associated to metabolism. The genes associated to metabolism-related GO terms have as common and central molecules different subunits of AMP activate protein kinase (AMPK). This energy-sensing enzyme is linked to different molecular functions that are altered in Alzheimer’s such as mitochondrial dysfunctions, alteration of autophagy pathways, lipid metabolism and circadian rhythm. In superior frontal gyrus, a enrichment in functional categories related to synaptic transmission was also found including neuropeptidergic systems involved not only in cognitive processes, but also in food intake and energy regulation. This advocates for a potential association to the suggested alteration of energy homeostasis in AD and to AMPK. In conclusion, this biomolecular network analysis indicate AMP-activated protein kinase (AMPK), a metabolic sensor, as a potential hub linking genetic perturbation with neurotransmitter and energy regulator and as a key protein regulating a series of brain function altered in AD.



Paper Details

Authors

L. Caberlotto,  M. Lauria,  P. Nguyen,  M. Scotti

Publication

Italian Society for Neuroscience

Language

English
.