摘要
Synaptic dysfunction is a precursor of cognitive decline and memory impairment in neurodegenerative diseases.The complement component 1q(C1q),and complement pathway contribute to synaptic loss and plasticity,leading to nerve damage.The walnut-derived peptide TWLPLPR(TW-7)has beneficial effect on nerve protection.However,its specific mechanisms are still not fully understood,particularly in C1q-mediated synaptic plasticity.We investigated the neuroprotective effects of TW-7,and the mechanism of C1q-mediated synaptic plasticity in hydrogen peroxide(H_(2)O_(2))-induced HT22 cells.Treatment with C1q gene plasmid overexpression in HT22 cells showed that TW-7 reduced C1q expression,thus decreasing complement three(C3)expression and increasing the presynaptic protein SYP and postsynaptic protein PSD95.Molecular docking confirmed that TW-7 binding to the recognition site of C1q and reduce synaptic loss.Furthermore,TW-7 inhibited local apoptosis and mediated the phosphoinositide 3-kinase/Programmable Logic Controller/IP3 receptor pathway to maintain intracellular Ca^(2+)homeostasis and improve synaptic plasticity.Our results suggest that TW-7 exerts a neuroprotective effect in HT22 cells by C1q-mediated synaptic plasticity.
基金
supported by the Science and Technology Research Project of Jilin Province(grant number:JJKH20220347KJ)
the Science and Technology Development Project of Jilin Province(grant number:20230202055NC).
