TheNrf2(Nuclearfactorerythroid2-relatedfactor2)signalingpathwayisacriticalcellulardefensemechanismagainstoxidativestress,playingapivotalroleinmaintainingredoxhomeostasisandprotectingcellsfromdamagecausedbyreactiveoxygenspecies(ROS)andelectrophiles.Underbasalconditions,Nrf2issequesteredinthecytoplasmbyitsrepressorKeap1(Kelch-likeECH-associatedprotein1)andtargetedforproteasomaldegradation.However,uponexposuretooxidativestressorelectrophilicinsults,Nrf2dissociatesfromKeap1,translocatestothenucleus,andbindstoantioxidantresponseelements(AREs)inthepromoterregionsofvariouscytoprotectivegenes.ThisactivationleadstotheupregulationofabatteryofphaseIIdetoxifyingenzymes,antioxidantproteins,andstress-responsivegenes,includinghemeoxygenase-1(HO-1),NAD(P)Hquinoneoxidoreductase1(NQO1),andglutathioneS-transferases(GSTs).TheNrf2pathwayhasgarneredsignificantattentionduetoitsimplicationsinvariouspathologicalconditions,suchasneurodegenerativediseases,cancer,inflammation,andaging,makingitapromisingtherapeutictargetforcombatingoxidativestress-relateddisorders.ThisreviewprovidesacomprehensiveoverviewofthemolecularmechanismsregulatingtheNrf2pathway,itsphysiologicalandpathologicalroles,andthepotentialtherapeuticstrategiestargetingNrf2fordiseaseintervention.
