| 1 | BMC Genomics 2013 -1 14 Suppl 5: S10 |
|---|---|
| PMID | 24564241 |
| Title | Analysis of schizophrenia and hepatocellular carcinoma genetic network with corresponding modularity and pathways: novel insights to the immune system. |
| Abstract | schizophrenic patients show lower incidences of cancer, implicating schizophrenia may be a protective factor against cancer. To study the genetic correlation between the two diseases, a specific PPI network was constructed with candidate genes of both schizophrenia and hepatocellular carcinoma. The network, designated schizophrenia-hepatocellular carcinoma network (SHCN), was analysed and cliques were identified as potential functional modules or complexes. The findings were compared with information from pathway databases such as KEGG, Reactome, PID and ConsensusPathDB. The functions of mediator genes from SHCN show immune system and cell cycle regulation have important roles in the eitology mechanism of schizophrenia. For example, the over-expressing schizophrenia candidate genes, SIRPB1, SYK and LCK, are responsible for signal transduction in cytokine production; immune responses involving IL-2 and TREM-1/DAP12 pathways are relevant for the etiology mechanism of schizophrenia. Novel treatments were proposed by searching the target genes of FDA approved drugs with genes in potential protein complexes and pathways. It was found that Vitamin A, retinoid acid and a few other immune response agents modulated by RARA and LCK genes may be potential treatments for both schizophrenia and hepatocellular carcinoma. This is the first study showing specific mediator genes in the SHCN which may suppress tumors. We also show that the schizophrenic protein interactions and modulation with cancer implicates the importance of immune system for etiology of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | BMC Genomics 2013 -1 14 Suppl 5: S10 |
| PMID | 24564241 |
| Title | Analysis of schizophrenia and hepatocellular carcinoma genetic network with corresponding modularity and pathways: novel insights to the immune system. |
| Abstract | schizophrenic patients show lower incidences of cancer, implicating schizophrenia may be a protective factor against cancer. To study the genetic correlation between the two diseases, a specific PPI network was constructed with candidate genes of both schizophrenia and hepatocellular carcinoma. The network, designated schizophrenia-hepatocellular carcinoma network (SHCN), was analysed and cliques were identified as potential functional modules or complexes. The findings were compared with information from pathway databases such as KEGG, Reactome, PID and ConsensusPathDB. The functions of mediator genes from SHCN show immune system and cell cycle regulation have important roles in the eitology mechanism of schizophrenia. For example, the over-expressing schizophrenia candidate genes, SIRPB1, SYK and LCK, are responsible for signal transduction in cytokine production; immune responses involving IL-2 and TREM-1/DAP12 pathways are relevant for the etiology mechanism of schizophrenia. Novel treatments were proposed by searching the target genes of FDA approved drugs with genes in potential protein complexes and pathways. It was found that Vitamin A, retinoid acid and a few other immune response agents modulated by RARA and LCK genes may be potential treatments for both schizophrenia and hepatocellular carcinoma. This is the first study showing specific mediator genes in the SHCN which may suppress tumors. We also show that the schizophrenic protein interactions and modulation with cancer implicates the importance of immune system for etiology of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Acta Physiol (Oxf) 2016 Jan 216: 42-89 |
| PMID | 25728499 |
| Title | Dopamine and T cells: dopamine receptors and potent effects on T cells, dopamine production in T cells, and abnormalities in the dopaminergic system in T cells in autoimmune, neurological and psychiatric diseases. |
| Abstract | Dopamine, a principal neurotransmitter, deserves upgrading to 'NeuroImmunotransmitter' thanks to its multiple, direct and powerful effects on most/all immune cells. Dopamine by itself is a potent activator of resting effector T cells (Teffs), via two independent ways: direct Teffs activation, and indirect Teffs activation by suppression of regulatory T cells (Tregs). The review covers the following findings: (i) T cells express functional dopamine receptors (DRs) D1R-D5R, but their level and function are dynamic and context-sensitive, (ii) DR membranal protein levels do not necessarily correlate with DR mRNA levels, (iii) different T cell types/subtypes have different DR levels and composition and different responses to dopamine, (iv) autoimmune and pro-inflammatory T cells and T cell leukaemia/lymphoma also express functional DRs, (v) dopamine (~10(-8) M) activates resting/naive Teffs (CD8(+) >CD4(+) ), (vi) dopamine affects Th1/Th2/Th17 differentiation, (vii) dopamine inhibits already activated Teffs (i.e. T cells that have been already activated by either antigen, mitogen, anti-CD3 antibodies cytokines or other molecules), (viii) dopamine inhibits activated Tregs in an autocrine/paracrine manner. Thus, dopamine 'suppresses the suppressors' and releases the inhibition they exert on Teffs, (ix) dopamine affects intracellular signalling molecules and cascades in T cells (e.g. ERK, LCK, Fyn, NF-?B, KLF2), (x) T cells produce dopamine (Tregs>Teffs), can release dopamine, mainly after activation (by antigen, mitogen, anti-CD3 antibodies, PKC activators or other), uptake extracellular dopamine, and most probably need dopamine, (xi) dopamine is important for antigen-specific interactions between T cells and dendritic cells, (xii) in few autoimmune diseases (e.g. multiple sclerosis/SLE/rheumatoid arthritis), and neurological/psychiatric diseases (e.g. Parkinson disease, Alzheimer's disease, schizophrenia and Tourette), patient's T cells seem to have abnormal DRs expression and/or responses to dopamine or production of dopamine, (xiii) drugs that affect the dopaminergic system have potent effects on T cells (e.g. dopamine=Intropin, L-dopa, bromocriptine, haloperidol, quinpirole, reserpine, pergolide, ecopipam, pimozide, amantadine, tetrabenazine, nomifensine, butaclamol). Dopamine-induced activation of resting Teffs and suppression of Tregs seem beneficial for health and may also be used for immunotherapy of cancer and infectious diseases. Independently, suppression of DRs in autoimmune and pro-inflammatory T cells, and also in cancerous T cells, may be advantageous. The review is relevant to Immunologists, Neurologists, Neuroimmunologists, Hematologists, Psychiatrists, Psychologists and Pharmacologists. |
| SCZ Keywords | schizophrenia, schizophrenic |