Mesocorticolimbic and Cardiometabolic Diseases—Two Faces of the Same Coin?
Abstract
:1. Introduction
2. Results
2.1. Performance of the Model
2.2. Targets for Treating MCL Disorders
2.3. Assessment of the Top 25 Control and Novel Targets
2.4. Putative Targets for MCL Disorders
3. Discussion
4. Materials and Methods
4.1. Selection of Disorders and Positive Control Targets
4.2. Knowledge-Based Approaches
4.3. Network-Based Approaches
4.4. Disease Similarity Approach
4.5. Integration of the Evidence
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Entrez ID | Gene Symbol | Gene Name | Score |
---|---|---|---|
1813 | DRD2 | dopamine receptor D2 | 4.2 |
4129 | MAOB | monoamine oxidase B | 7.3 |
6531 | SLC6A3 | solute carrier family 6 (neurotransmitter transporter), member 3 | 10.5 |
4128 | MAOA | monoamine oxidase A | 16.0 |
3358 | HTR2C | 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled | 18.7 |
3351 | HTR1B | 5-hydroxytryptamine (serotonin) receptor 1B, G protein-coupled | 19.6 |
1814 | DRD3 | dopamine receptor D3 | 20.4 |
6530 | SLC6A2 | solute carrier family 6 (neurotransmitter transporter), member 2 | 21.5 |
5970 | RELA | v-rel avian reticuloendotheliosis viral oncogene homolog A | 25.0 |
1137 | CHRNA4 | cholinergic receptor, nicotinic, alpha 4 (neuronal) | 26.1 |
9177 | HTR3B | 5-hydroxytryptamine (serotonin) receptor 3B, ionotropic | 32.6 |
320 | APBA1 | amyloid beta (A4) precursor protein-binding, family A, member 1 | 33.1 |
2904 | GRIN2B | glutamate receptor, ionotropic, N-methyl D-aspartate 2B | 39.3 |
4803 | NGF | nerve growth factor (beta polypeptide) | 40.5 |
3352 | HTR1D | 5-hydroxytryptamine (serotonin) receptor 1D, G protein-coupled | 42.8 |
1815 | DRD4 | dopamine receptor D4 | 44.4 |
321 | APBA2 | amyloid beta (A4) precursor protein-binding, family A, member 2 | 46.1 |
2915 | GRM5 | glutamate receptor, metabotropic 5 | 46.5 |
3630 | INS | insulin | 47.7 |
3350 | HTR1A | 5-hydroxytryptamine (serotonin) receptor 1A, G protein-coupled | 49.1 |
3354 | HTR1E | 5-hydroxytryptamine (serotonin) receptor 1E, G protein-coupled | 50.6 |
3357 | HTR2B | 5-hydroxytryptamine (serotonin) receptor 2B, G protein-coupled | 60.7 |
170572 | HTR3C | 5-hydroxytryptamine (serotonin) receptor 3C, ionotropic | 73.7 |
2906 | GRIN2D | glutamate receptor, ionotropic, N-methyl D-aspartate 2D | 78.4 |
2668 | GDNF | glial cell derived neurotrophic factor | 91.2 |
Molecular Function | r | R | n | N | p Value |
---|---|---|---|---|---|
serotonin binding | 7 | 25 | 11 | 15,288 | 4.08 × 10−18 |
amine binding | 7 | 25 | 13 | 15,288 | 2.12 × 10−17 |
drug binding | 11 | 25 | 130 | 15,288 | 4.4 × 10−17 |
serotonin receptor activity | 7 | 25 | 15 | 15,288 | 7.93 × 10−17 |
G-protein coupled amine receptor activity | 7 | 25 | 42 | 15,288 | 3.23 × 10−13 |
transmembrane signaling receptor activity | 14 | 25 | 1196 | 15,288 | 5.86 × 10−10 |
dopamine binding | 4 | 25 | 10 | 15,288 | 1.16 × 10−9 |
signaling receptor activity | 14 | 25 | 1299 | 15,288 | 1.74 × 10−9 |
signal transducer activity | 15 | 25 | 1617 | 15,288 | 2.55 × 10−9 |
molecular transducer activity | 15 | 25 | 1617 | 15,288 | 2.55 × 10−9 |
dopamine neurotransmitter receptor activity, coupled via Gi/Go | 3 | 25 | 3 | 15,288 | 3.86 × 10−9 |
catecholamine binding | 4 | 25 | 14 | 15,288 | 5.5 × 10−9 |
G-protein coupled receptor activity | 11 | 25 | 812 | 15,288 | 1.99 × 10−8 |
receptor activity | 14 | 25 | 1583 | 15,288 | 2.28 × 10−8 |
dopamine neurotransmitter receptor activity | 3 | 25 | 5 | 15,288 | 3.85 × 10−8 |
extracellular ligand-gated ion channel activity | 5 | 25 | 74 | 15,288 | 1.14 × 10−7 |
excitatory extracellular ligand-gated ion channel activity | 4 | 25 | 49 | 15,288 | 1.12 × 10−6 |
ligand-gated channel activity | 5 | 25 | 145 | 15,288 | 3.27 × 10−6 |
ligand-gated ion channel activity | 5 | 25 | 145 | 15,288 | 3.27 × 10−6 |
neurotransmitter binding | 3 | 25 | 24 | 15,288 | 7.64 × 10−6 |
Entrez ID | Gene Symbol | Gene Name | Score |
---|---|---|---|
1803 | DPP4 | dipeptidyl-peptidase 4 | 14.8 |
3359 | HTR3A | 5-hydroxytryptamine (serotonin) receptor 3A, ionotropic | 17.8 |
5468 | PPARG | peroxisome proliferator-activated receptor gamma | 29.5 |
1385 | CREB1 | cAMP responsive element binding protein 1 | 45.7 |
775 | CACNA1C | calcium channel, voltage-dependent, L type, alpha 1C subunit | 48.1 |
5443 | POMC | proopiomelanocortin | 51.9 |
2905 | GRIN2C | glutamate receptor, ionotropic, N-methyl D-aspartate 2C | 58.2 |
2903 | GRIN2A | glutamate receptor, ionotropic, N-methyl D-aspartate 2A | 61.9 |
6616 | SNAP25 | synaptosomal-associated protein, 25 kDa | 65.5 |
9900 | SV2A | synaptic vesicle glycoprotein 2A | 69.6 |
776 | CACNA1D | calcium channel, voltage-dependent, L type, alpha 1D subunit | 73.2 |
781 | CACNA2D1 | calcium channel, voltage-dependent, alpha 2/delta subunit 1 | 73.9 |
783 | CACNB2 | calcium channel, voltage-dependent, beta 2 subunit | 74.1 |
4842 | NOS1 | nitric oxide synthase 1 (neuronal) | 81.5 |
1636 | ACE | angiotensin I converting enzyme | 82.1 |
801 | CALM1 | calmodulin 1 (phosphorylase kinase, delta) | 83.0 |
784 | CACNB3 | calcium channel, voltage-dependent, beta 3 subunit | 95.1 |
322 | APBB1 | amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65) | 97.4 |
59285 | CACNG6 | calcium channel, voltage-dependent, gamma subunit 6 | 97.4 |
9254 | CACNA2D2 | calcium channel, voltage-dependent, alpha 2/delta subunit 2 | 98.3 |
19 | ABCA1 | ATP-binding cassette, sub-family A (ABC1), member 1 | 98.9 |
6285 | S100B | S100 calcium binding protein B | 100.7 |
185 | AGTR1 | angiotensin II receptor, type 1 | 101.7 |
773 | CACNA1A | calcium channel, voltage-dependent, P/Q type, alpha 1A subunit | 107.0 |
6570 | SLC18A1 | solute carrier family 18 (vesicular monoamine transporter), member 1 | 107.7 |
Molecular Function | r | R | n | N | p-Value |
---|---|---|---|---|---|
voltage-gated cation channel activity | 11 | 25 | 138 | 15,288 | 8.66 × 10−17 |
voltage-gated calcium channel activity | 8 | 25 | 35 | 15,288 | 3.35 × 10−16 |
voltage-gated ion channel activity | 11 | 25 | 188 | 15,288 | 2.78 × 10−15 |
voltage-gated channel activity | 11 | 25 | 188 | 15,288 | 2.78 × 10−15 |
cation channel activity | 12 | 25 | 289 | 15,288 | 6.93 × 10−15 |
ion gated channel activity | 12 | 25 | 323 | 15,288 | 2.63 × 10−14 |
gated channel activity | 12 | 25 | 323 | 15,288 | 2.63 × 10−14 |
calcium channel activity | 9 | 25 | 109 | 15,288 | 6.32 × 10−14 |
calcium ion transmembrane transporter activity | 9 | 25 | 128 | 15,288 | 2.77 × 10−13 |
ion channel activity | 12 | 25 | 415 | 15,288 | 5.17 × 10−13 |
substrate-specific channel activity | 12 | 25 | 425 | 15,288 | 6.85 × 10−13 |
high voltage-gated calcium channel activity | 5 | 25 | 9 | 15,288 | 9.58 × 10−13 |
passive transmembrane transporter activity | 12 | 25 | 450 | 15,288 | 1.34 × 10−12 |
channel activity | 12 | 25 | 450 | 15,288 | 1.34 × 10−12 |
divalent inorganic cation transmembrane transporter activity | 9 | 25 | 155 | 15,288 | 1.59 × 10−12 |
transmembrane transporter activity | 15 | 25 | 972 | 15,288 | 1.81 × 10−12 |
cation transmembrane transporter activity | 13 | 25 | 618 | 15,288 | 2.26 × 10−12 |
ion transmembrane transporter activity | 14 | 25 | 825 | 15,288 | 4.08 × 10−12 |
metal ion transmembrane transporter activity | 11 | 25 | 401 | 15,288 | 1.13 × 10−11 |
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Papp, C.; Mikaczo, A.; Szabo, J.; More, C.E.; Viczjan, G.; Gesztelyi, R.; Zsuga, J. Mesocorticolimbic and Cardiometabolic Diseases—Two Faces of the Same Coin? Int. J. Mol. Sci. 2024, 25, 9682. https://doi.org/10.3390/ijms25179682
Papp C, Mikaczo A, Szabo J, More CE, Viczjan G, Gesztelyi R, Zsuga J. Mesocorticolimbic and Cardiometabolic Diseases—Two Faces of the Same Coin? International Journal of Molecular Sciences. 2024; 25(17):9682. https://doi.org/10.3390/ijms25179682
Chicago/Turabian StylePapp, Csaba, Angela Mikaczo, Janos Szabo, Csaba E. More, Gabor Viczjan, Rudolf Gesztelyi, and Judit Zsuga. 2024. "Mesocorticolimbic and Cardiometabolic Diseases—Two Faces of the Same Coin?" International Journal of Molecular Sciences 25, no. 17: 9682. https://doi.org/10.3390/ijms25179682