TrkB agonist prodrug R13 (R13) is a prodrug form of the tropomyosin-related kinase B (TrkB) activator 7,8-dihydroxyflavone.1 Oral administration of R13 (43.6 mg/kg per day) increases hippocampal phosphorylated levels of TrkB, ERK, and Akt in the 5XFAD transgenic mouse model of Alzheimer's disease. It decreases the number of malformed neurons and increases the number of neurons and active synapses in the hippocampus in 5XFAD mice. R13 decreases the number of plaques and levels of amyloid-β (1-40) (Aβ40) in the hippocampus and frontal cortex and escape latency in the Morris water maze in 5XFAD mice. It reduces the levels and activity of δ-secretase, also known as asparagine endopeptidase (Aep) and legumain, and the levels of Il-6, Tnf-α, and Il-1β in brain homogenates from 5XFAD mice.
References:
[1]. Chen, C., Wang, Z., Zhang, Z., et al.The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer's diseaseProc. Natl. Acad. Sci. U S A115(3)578-583(2018).