The protective effect of epigallocatechin gallate on the oligodendrocyte damage in Alzheimer's disease via the Shh signaling pathway
PENG Huan
MENG Lin
HU Fengrui
Abstract：Objective To investigate the potential protective properties of epigallocatechin gallate(EGCG)against the oligodendrocyte damage in Alzheimer's disease(AD),by regulating the Sonic Hedgehog(Shh)pathway,and to illustrate the underlying mechanisms.Methods Mouse hippocampus cell line HT22(HT22-AD)with stable overexpression of human amyloid precursor protein(hAPP)and human presenilin-1(h-PSEN1)were generated.The oligodendrocyte cell line OLN-93 was induced in the supernatant of HT22-AD or HT22-AD induced with EGCG.The influence of h-APP and h-PSEN1 dysregulations,as well as EGCG on OLN-93 cells was explored.Results The Shh ligand was significantly upregulated in HT22-AD cells(P＜0.05).OLN-93 cells induced with HT22-AD cell supernatant presented atrophy of cell processes(P＜0.05).The downstream proteins Sufu was significantly downregulated,while Gli1 was upregulated(P＜0.05).Cell skeleton molecule Rho-associated kinase 2(ROCK2)was upregulated.Apoptosis proteins Bcl-2 was downregulated,while Bax was upregulated.Shh was downregulated in HT22-AD cells(P＜0.05).Compared with OLN-93 cells induced with supernatant of HT22-AD cells,those in supernatant of EGCG-induced HT22-AD cells showed prolonged cell processes,upregulation of Sufu and Bcl-2,and downregulation of Gli1,Rock2 and Bax(P＜0.05).Conclusion EGCG has a protective influence on the atrophy of protrusions and apoptotic damage in OLN-93 cells triggered by the HT22-AD model.This protective mechanism is associated with the down-regulation of the Shh pathway.
Keywords：Alzheimer's diseaseepigallocatechin gallate(EGCG)OLN-93 cellsHT22 cellsSonic Hedgehog signaling pathway
Publication Date：2025-05-26
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 715-720,727 )