Neuron survival is associated with nerve growth factor (NGF) and its interaction with high-affinity (TrkA) and low-affinity (p75NTR) receptors. NGF induces the formation of a persistent endosomal signaling complex containing TrkA, MAPK, and Rap-1 (Ras GTPase that activates MEK/MAPK indefinitely). TrkA stimulated by NGF transiently activates Ras on the plasma membrane . The activation of the JNK signaling pathway and the suppression of the PI3K, Akt, and ERK signaling pathways may contribute to ZIKV-induced neuronal cell death(1). Clathrin-mediated trafficking appears to be critical for transferring information from TrkA receptor activation to Ras-MAPK pathway participation . Glucose variations trigger apoptosis by modulating the TrkA/p75NTR and PI3K/AKT pathways . The expression of the dominant-negative form of PI 3-kinase or Akt promotes apoptosis in the presence of NGF . By boosting proNGF and lowering mNGF, Akt, TrkA, p75 NTR, and p17, NGF and PI3K inhibition results in enhanced neuronal cell death . This study discovered that endosomal signals from Zika E/TrkA can be transferred to the neuron cell body. Zika infection can result in aberrant PI3K signaling, which can result in neuronal cell death.