INS and Alzheimer disease: The drug reduced Aβ toxicity without over-regulating insulin signaling, presenting a promising strategy for AD prevention or treatment.556 In a phase I study (NCT05077501), the novel Trk receptor PAM ACD856 (58).557 demonstrated good safety and tolerability, as well as favorable pharmacokinetic properties, potentially benefiting neurotrophic factor signaling.558 Several reviews70,559–561 have extensively summarized allosteric modulation strategies targeting other proteins such as GSK-3β, NMDARs, AMPA receptors, and RIPK1 (Fig. 7a).