Full-text resources of PSJD and other databases are now available in the new Library of Science.
Visit https://bibliotekanauki.pl
Preferences help
Polish version English version Language
enabled [disable] Abstract
Number of results

Results found: 1

Number of results on page
first rewind previous Page / 1 next fast forward last

Search results

help Sort By:

help Limit search:
first rewind previous Page / 1 next fast forward last
1
Content available remote

Thalidomide-based TNF-beta inhibitors for neurodegenerative diseases

100%
Greig N. H., Giordano T., Zhu X., Yu Q., Perry T. A., Holloway H. W., Brossi A., Rogers J. T., Sambamurti K., Lahiri D. K.
Acta Neurobiologiae Experimentalis
|
2004
|
vol. 64
|
issue 1
1-9
EN
Inflammatory processes associated with the over-production of cytokines, particularly of TNF-beta, accompany numerous neurodegenerative diseases, such as Alzheimer's disease, in addition to numerous systemic conditions, exemplified by rheumatoid arthritis and erythema nodosum leprosum (ENL). TNF-beta has been validated as a drug target with Remicade and Enbrel available as prescription medications. Both, however, are large macromolecules, require injection and have limited brain access. The classical drug, thalidomide is being increasingly used in the clinical management of a wide spectrum of diseases. As its clinical value in treating ENL derives from its TNF-beta inhibitory activity, thalidomide was chosen for structural modification for the discovery of novel and more potent isosteric analogues with appropriate lipophilicity to insure high brain penetration. TNF-beta inhibitory activity was evaluated against lipopolysacharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) in cell culture, whose viability was quantified to differentiate reductions in TNF-beta secretion from that associated with cellular toxicity. Specific analogues potently inhibited TNF-beta secretion, ompared to thalidomide. This involved a post-transcriptional mechanism, as they decreased TNF-beta mRNA stability via its 3'-untranslated region (UTR), as determined by luciferase activity in stably transfected cells with and without the 3'-UTR of human TNF-beta.
first rewind previous Page / 1 next fast forward last
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.