Neuroprotective mechanism of walnut-derived peptide via C1q-mediated synaptic plasticity in HT22 cells

Abstract

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 (H2O2)-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 Ca2+ homeostasis and improve synaptic plasticity. Our results suggest that TW-7 exerts a neuroprotective effect in HT22 cells by C1q-mediated synaptic plasticity.