Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review analyses the accumulating evidence from psychological, psychophysiological, neurobiological and cognitive studies suggesting that the disease-avoidance emotion of disgust is a predominant emotion experienced in a number of psychopathologies. Current evidence suggests that disgust is significantly related to small animal phobias (particularly spider phobia), blood-injection-injury phobia and obsessive-compulsive disorder contamination fears, and these are all disorders that have primary disgust elicitors as a significant component of their psychopathology. Disgust propensity and sensitivity are also significantly associated with measures of a number of other psychopathologies, including eating disorders, sexual dysfunctions, hypochondriasis, height phobia, claustrophobia, separation anxiety, agoraphobia and symptoms of schizophrenia--even though many of these psychopathologies do not share the disease-avoidance functionality that characterizes disgust. There is accumulating evidence that disgust does represent an important vulnerability factor for many of these psychopathologies, but when disgust-relevant psychopathologies do meet the criteria required for clinical diagnosis, they are characterized by significant levels of both disgust and fear/anxiety. Finally, it has been argued that disgust may also facilitate anxiety and distress across a broad range of psychopathologies through its involvement in more complex human emotions such as shame and guilt, and through its effect as a negative affect emotion generating threat-interpretation biases.
 ...
PMID:Disgust: the disease-avoidance emotion and its dysfunctions. 2204 21

Neuronal glycoprotein M6a is involved in neuronal plasticity, promoting neurite and filopodia outgrowth and, likely, synaptogenesis. Polymorphisms in the human M6a gene GPM6A have recently been associated with mental illnesses such as schizophrenia, bipolar disorders, and claustrophobia. Nevertheless, the molecular bases underlying these observations remain unknown. We have previously documented that, to induce filopodia formation, M6a depends on the association of membrane lipid microdomains and the activation of Src and mitogen-activated protein kinase kinases. Here, in silico analysis of the phosphorylation of tyrosine 251 (Y251) at the C-terminus of M6a showed that it could be a target of Src kinases. We examined whether phosphorylation of M6a at Y251 affects neurite and filopodia outgrowth and the targets involved in its signal propagation. This work provides evidence that the Src kinase family and the phosphatidylinositide 3-kinase (PI3K), but not Ras, participate in M6a signal cascade leading to neurite/filopodia outgrowth in hippocampal neurons and murine neuroblastoma N2a cells. Phosphorylation of M6a at Y251 is essential only for neurite outgrowth by the PI3K/AKT-mediated pathway and, moreover, rescues the inhibition caused by selective Src inhibitor and external M6a monoclonal antibody treatment. Thus, we suggest that phosphorylation of M6a at Y251 is critical for a specific stage of neuronal development and triggers redundant signaling pathways leading to neurite extension.
 ...
PMID:Tyrosine 251 at the C-terminus of neuronal glycoprotein M6a is critical for neurite outgrowth. 2524 28

Neuronal glycoprotein M6a belongs to the tetraspan proteolipid protein (PLP) family. Mutations in GPM6A gene have been related to mental disorders like schizophrenia, bipolar disorders and claustrophobia. M6a is expressed mainly in neuronal cells of the central nervous system and it has been extensively related to neuronal plasticity. M6a induces neuritogenesis and axon/filopodium outgrowth; however its mechanism of action is still unresolved. We recently reported that the integrity of the transmembrane domains (TMDs) 2 and 4 are critical for M6a filopodia induction. There is also experimental data suggesting that M6a might be involved in synaptogenesis. In this regard, we have previously determined that M6a is involved in filopodia motility, a process that is described in the first step of the filopodial model for synaptogenesis. In this work we analyzed the possible involvement of M6a in synaptogenesis and spinogenesis, and evaluated the effect of two non-synonymous SNPs present in the coding region of TMD2-GPM6A in these processes. The results showed that endogenous M6a colocalized with both, pre-synaptic (synaptophysin) and post-synaptic (NMDA-R1), markers along of neuronal soma and dendrites. M6a-overexpressing neurons displayed an increased number of synaptophysin and NMDA-R1 puncta and, also, an increased number of colocalization puncta between both markers. Conversely, the number of synaptic puncta markers in neurons expressing nsSNP variants was similar to those of control neurons. Overexpression of M6a is accompanied by an increase in spine density, particularly in mature spines, as compared with neurons expressing mGFP or GPM6A nsSNP variants. Taken together, these results suggest that M6a contributes positively to spine and, likely, synapse formation.
 ...
PMID:Evidence for a role of glycoprotein M6a in dendritic spine formation and synaptogenesis. 2779 98