Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism
02.03.2015
Menzfeld C, John M, van Rossum D, Regen T, Scheffel J, Janova H, Götz A, Ribes S, Nau R, Borisch A, Boutin P, Neumann K, Bremes V, Wienands J, Reichardt HM, Lühder F, Tischner D, Waetzig V, Herdegen T, Teismann P, Greig I, Müller M, Pukrop T, Mildner A, Kettenmann H, Brück W, Prinz M, Rotshenker S, Weber MS, Hanisch UK.
Glia. 2015;63(6):1083-99
The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Its anti-inflammatory potential and especially interference with TLR signaling thus rely on a dual mechanism encompassing BTK and a novel MN-sensitive target. Both principles bear great potential for the therapeutic management of disturbed innate and adaptive immune functions.
