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Novel drug target identification for the treatment of dementia using multi-relational association mining.

Nguyen TP, Priami C, Caberlotto L - Sci Rep (2015)

Bottom Line: Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance.Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor.Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies.

View Article: PubMed Central - PubMed

Affiliation: 1] The Microsoft Research, University of Trento Centre for Computational Systems Biology (COSBI), Piazza Manifattura 1, 38068, Rovereto, Italy [2] Life Sciences Research Unit, University of Luxembourg, 162 A, avenue de la Faïencerie, L-1511 Luxembourg.

ABSTRACT
Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia.

No MeSH data available.


Related in: MedlinePlus

Summary of statistically significant Gene Ontology biological processes functional annotation corresponding to the putative DT list as obtained from REVIGO.Nodes are GO terms and edges represent the strongest GO terms pairwise similarity. Colors represent the p-values (low values in green, high in red). Only significant GO terms are shown (P < 0.001).
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f6: Summary of statistically significant Gene Ontology biological processes functional annotation corresponding to the putative DT list as obtained from REVIGO.Nodes are GO terms and edges represent the strongest GO terms pairwise similarity. Colors represent the p-values (low values in green, high in red). Only significant GO terms are shown (P < 0.001).

Mentions: A significant enrichment in Alzheimer disease-amyloid secretase pathway (Panther:P00003), the hallmark of Alzheimer’s disease42 was evidenced by pathway analysis of the predicted DTs giving further support to the relevance of our findings to dementia. In addition, a significant enrichment in biological functions associated to long-term potentiation (Fig. 6), a phenomenon related to synaptic plasticity, one of the most important cellular mechanisms that underlies learning and memory, was also found. Proteins involved are PKC, PKA, ERK1/2, Rsk, and CAMK2 (Supplementary File 3). These results are in line with recent studies suggesting that activation of protein kinase C could have potential for the treatment of dementia43.


Novel drug target identification for the treatment of dementia using multi-relational association mining.

Nguyen TP, Priami C, Caberlotto L - Sci Rep (2015)

Summary of statistically significant Gene Ontology biological processes functional annotation corresponding to the putative DT list as obtained from REVIGO.Nodes are GO terms and edges represent the strongest GO terms pairwise similarity. Colors represent the p-values (low values in green, high in red). Only significant GO terms are shown (P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495601&req=5

f6: Summary of statistically significant Gene Ontology biological processes functional annotation corresponding to the putative DT list as obtained from REVIGO.Nodes are GO terms and edges represent the strongest GO terms pairwise similarity. Colors represent the p-values (low values in green, high in red). Only significant GO terms are shown (P < 0.001).
Mentions: A significant enrichment in Alzheimer disease-amyloid secretase pathway (Panther:P00003), the hallmark of Alzheimer’s disease42 was evidenced by pathway analysis of the predicted DTs giving further support to the relevance of our findings to dementia. In addition, a significant enrichment in biological functions associated to long-term potentiation (Fig. 6), a phenomenon related to synaptic plasticity, one of the most important cellular mechanisms that underlies learning and memory, was also found. Proteins involved are PKC, PKA, ERK1/2, Rsk, and CAMK2 (Supplementary File 3). These results are in line with recent studies suggesting that activation of protein kinase C could have potential for the treatment of dementia43.

Bottom Line: Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance.Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor.Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies.

View Article: PubMed Central - PubMed

Affiliation: 1] The Microsoft Research, University of Trento Centre for Computational Systems Biology (COSBI), Piazza Manifattura 1, 38068, Rovereto, Italy [2] Life Sciences Research Unit, University of Luxembourg, 162 A, avenue de la Faïencerie, L-1511 Luxembourg.

ABSTRACT
Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia.

No MeSH data available.


Related in: MedlinePlus