Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Multiple sclerosis is a disease characterised by demyelination of axons in the central nervous system. The atypical antipsychotic drug clozapine has been shown to attenuate disease severity in experimental autoimmune encephalomyelitis (EAE), a mouse model that is useful for the study of multiple sclerosis. However, the mechanism of action by which clozapine reduces disease in EAE is poorly understood. To better understand how clozapine exerts its protective effects, we investigated the underlying signalling pathways by which clozapine may reduce immune cell migration by evaluating chemokine and dopamine receptor-associated signalling pathways. We found that clozapine inhibits migration of immune cells by reducing chemokine production in microglia cells by targeting NF-κB phosphorylation and promoting an anti-inflammatory milieu. Furthermore, clozapine directly targets immune cell migration by changing Ca levels within immune cells and reduces the phosphorylation of signalling protein AKT. Linking these pathways to the antagonising effect of clozapine on dopamine and serotonin receptors, we provide insight into how clozapine alters immune cells migration by directly targeting the underlying migration-associated pathways.
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Source |
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http://dx.doi.org/10.1016/j.cellsig.2022.110449 | DOI Listing |
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