Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Traumatic SCI directly damages the cell bodies and/or processes of neurons and triggers a series of endogenous processes, including neuroinflammatory response and reactive astrogliosis. In this study, we found that triptolide, one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, inhibited astrogliosis and inflammation and promoted spinal cord repair. Triptolide was shown to prevent astrocytes from reactive activation by blocking the JAK2/STAT3 pathway in vitro and in vivo. Furthermore, astrocytic gliosis and glial scar were greatly reduced in injured spinal cord treated with triptolide. Triptolide treatment was also shown to decrease the ED-1 or CD11b-positive inflammatory cells at the lesion site. Using neurofilament staining and anterograde tracing, a significantly greater number of regenerative axons were observed in the triptolide-treated rats. Importantly, behavioral tests revealed that injured rats receiving triptolide had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan open-field scoring, grid-walk, and foot-print analysis. These results suggested that triptolide promoted axon regeneration and locomotor recovery by attenuating glial scaring and inflammation, and shed light on the potential therapeutic benefit for SCI.
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PMID:Triptolide promotes spinal cord repair by inhibiting astrogliosis and inflammation. 2015 20

Wilson's Disease (WD), a copper transport disorder caused by a genetic defect in the ATP7B gene, has been a long time strong candidate for newborn screening (NBS), since early interventions can give better results by preventing irreversible neurological disability or liver cirrhosis. Several previous pilot studies measuring ceruloplasmin (CP) in infants or children showed that this marker alone was insufficient to meet the universal screening for WD. WD results from mutations that cause absent or markedly diminished levels of ATP7B. Therefore, ATP7B could serve as a marker for the screening of WD, if the protein can be detected from dried blood spots (DBS). This study demonstrates that the immuno-SRM platform can quantify ATP7B in DBS in the picomolar range, and that the assay readily distinguishes affected cases from normal controls (p < 0.0001). The assay precision was <10% CV, and the protein was stable for a week in DBS at room temperature. These promising proof-of-concept data open up the possibility of screening WD in newborns and the potential for a multiplexed assay for screening a variety of congenital disorders using proteins as biomarkers in DBS.
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PMID:Quantification of ATP7B Protein in Dried Blood Spots by Peptide Immuno-SRM as a Potential Screen for Wilson's Disease. 2793 10

Increasing evidence suggests that B cells contribute both to the regulation of normal autoimmunity and to the pathogenesis of immune mediated diseases, including multiple sclerosis (MS). B cells in MS are skewed toward a pro-inflammatory profile, and contribute to MS pathogenesis by antibody production, antigen presentation, T cells stimulation and activation, driving autoproliferation of brain-homing autoreactive CD4+ T cells, production of pro-inflammatory cytokines, and formation of ectopic meningeal germinal centers that drive cortical pathology and contribute to neurological disability. The recent interest in the key role of B cells in MS has been evoked by the profound anti-inflammatory effects of rituximab, a chimeric monoclonal antibody (mAb) targeting the B cell surface marker CD20, observed in relapsing-remitting MS. This has been reaffirmed by clinical trials with less immunogenic and more potent B cell-depleting mAbs targeting CD20 - ocrelizumab, ofatumumab and ublituximab. Ocrelizumab is also the first disease-modifying drug that has shown efficacy in primary-progressive MS, and is currently approved for both indications. Another promising approach is the inhibition of Bruton's tyrosine kinase, a key enzyme that mediates B cell activation and survival, by agents such as evobrutinib. On the other hand, targeting B cell cytokines with the fusion protein atacicept increased MS activity, highlighting the complex and not fully understood role of B cells and humoral immunity in MS. Finally, all other approved therapies for MS, some of which have been designed to target T cells, have some effects on the frequency, phenotype, or homing of B cells, which may contribute to their therapeutic activity.
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PMID:Therapies for multiple sclerosis targeting B cells. 3104 80