Use of STAT1 inhibitors in the treatment of brain I/R injury and neurodegenerative diseases.
In the etiology of brain injury associated to ischemia/reperfusion (I/R) and neurodegenerative diseases, a critical involvement of excessive activation of signal transducer and activator of transcription 1 (STAT1) and successive induction of iNOS expression has widely been evidenced. Any compound capable to down-regulate STAT1 activation seems to represent a new, promising anti-inflammatory drug. Among plant compounds, only a few have shown to possess anti-STAT1 activity. Among them, epigallocatechin-3-gallate (EGCG), the main polyphenol present in green tea leaves, efficiently protects heart from I/R injury and this action is strictly correlated to its anti-STAT1 property. Hyperforin, the non-polyphenolic compound present in St. John's wort, attenuates &beta;-cell death induced by interferon-&gamma; (IFN-&gamma;) by strongly down-regulating STAT1 activation. STAT1, therefore, seems to represent a new molecular target of the protective treatment also against brain injury associated to a number of brain pathologies. Either understanding the molecular mechanism of anti-STAT1 action of these compounds or identification of other anti-STAT1 compounds are urged.
Ebner
F H
FH
Dipartimento di Scienze Morfologico-Biomediche, Università di Verona, Verona, Italy.
Mariotto
S
S
Darra
E
E
Suzuki
H
H
Cavalieri
E
E
D000818:Animals; D001921:Brain / Q000473:pathology*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000627:therapeutic use; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D015394:Molecular Structure; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use; D010696:Phloroglucinol / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D013729:Terpenes / Q000737:chemistry / Q000627:therapeutic use
D001643:Bridged Bicyclo Compounds; D018696:Neuroprotective Agents; D050794:STAT1 Transcription Factor; D013729:Terpenes; D002392:Catechin; C045651:epigallocatechin gallate; D010696:Phloroglucinol; D053612:Janus Kinases; C001654:hyperforin