Synaptic loss and subsequent neuronal death are paramount pathology in neurodegeneration. Therapeutic interventions that restore or prevent such events hold promise as disease modifying therapies. Brain derived neurotrophic factor (BDNF) is the best known neurotrophin to strengthen synaptic plasticity and promote neuron survival via its cognate receptor TrkB. Due to druggability limitations, however, BDNF failed to demonstrate effective neuroprotection in the clinic. Development of agents that can activate TrkB efficaciously in vivo became an attractive therapeutic pursuit. 4B Tech has discovered a series of potent and selective TrkB agonistic mAbs (TrkB agoAbs), which bind/activate TrkB with superior pharmaceutical properties to BDNF. Unlike BDNF, the TrkB agoAbs’ action is highly specific with no detectable cross-reactivity with p75, a co-receptor of BDNF and the activation of which would cause detrimental effects. The therapeutic potential of TrkB agoAbs has been demonstrated in a wide range of preclinical disease models and is on the way to be validated in the clinic.