产品描述:
LM22A-4 is a brain-derived neurotrophic factor (BDNF) mimetic and agonist of the receptor tropomyosin-related kinase B (TrkB; IC50 = 47 nM in a fluorescence anisotropy assay).{38767} It selectively inhibits BDNF binding to 3T3 cells expressing TrkB over those expressing TrkA, TrkC, or p75NTR. In vitro, LM22A-4 increases survival of hippocampal neurons via activation of TrkB as well as Akt and ERK downstream pro-survival signaling pathways. In vivo, LM22A-4 increases dwell time in an accelerating rotarod task, indicating improved motor learning in a rat model of traumatic brain injury. LM22A-4 restores TrkB phosphorylation in the medulla and pons and breathing frequency to wild-type levels in a mouse model of Rett syndrome when administered at a dose of 50 mg/kg.{38768} It reduces neurite degeneration, formation of intranuclear huntingtin aggregates, and improves downward climbing and grip strength in mouse models of Huntington's disease.{38769} LM22A-4 (0.22 mg/kg) also improves limb swing speed and accelerates return to normal gait accuracy in a mouse model of hypoxic-ischemic stroke.{38770}