Improvement of Key Molecular Events Linked to Alzheimer’s Disease Pathology Using Postbiotics

BULACIOS, GABRIELA; CATALDO, PABLO; NAJA, JOSEFINA; POSSE DE CHAVEZ, ELENA; TARANTO, MARIA PIA; MINAHK, CARLOS; HEBERT, ELVIRA MARÍA; SAAVEDRA, LUCILA

ACS Omega

American Chemical Society

Año: 2023 vol. 8 p. 48042 - 48049

In thepast 50years, lifeexpectancyhas increasedbymore than20 years.Oneconsequenceof this increaseinlongevityistheriseofage-relateddiseases suchasdementia.Alzheimer’sdisease(AD) is themost commonformofdementia, accounting for60−70%of cases.ADpathogenesis isnot restrictedto theneuronal compartment but includes strong interactions with other brain cells, particularly microgliatriggeringthereleaseof inflammatorymediators,whichcontributetodisease progression and severity. There is growing evidence revealing the diverse clinical benefits of postbiotics inmany prevalent conditions, including neurodegenerative diseases.Here,we testedtheabilityof bacterial conditionedmedia(BCM)derived fromselectedlacticacidbacteria(LAB)strainstoregulatecoremechanismsrelevantto ADpathophysiologyinthemicrogliacell lineBV-2.LevilactobacillusbrevisCRL2013, chosen for its efficient productionof theneurotransmitterGABA, andLactobacillus delbrueckii subsp. lactisCRL581, known for its anti-inflammatoryproperties, were selectedalongsideEnterococcusmundtiiCRL35,aLABstrainthatcansignificantlymodulatecytokineproduction.BCMfromall3 strainsdisplayedantioxidant capabilities, reducingoxidative stress triggeredbybeta-amyloidoligomers (oAβ1−42). Additionally, BCMeffectivelymitigated the expressionof inflammatory cytokines, namely, TNF-α, IL-1β, and IL-6 triggeredby oAβ1−42. Furthermore,ourstudyidentifiedthatBCMfromCRL581inhibittheactivityofacetylcholinesterase(AChE),acrucialenzymein ADprogression, inbothhumanerythrocytesandmousebraintissues.Notably, theinhibitoryeffectwasmediatedbylow-molecularweightcomponentsoftheBCM.L.delbrueckiisubsp. lactisCRL581emergedasafavorablecandidateforproductionofpostbiotics withpotentialbenefitsforADtherapysinceitdemonstratedpotentantioxidantactivity,reductionofcytokineexpression,andpartial AChEinhibition.Ontheotherhand,E.mundtiiCRL35showedthat theantioxidant activity failedtoinhibitAChEandcaused inductionof iNOSexpression, renderingitunsuitableasapotential therapeuticforAD.Thisstudyunveilsthepotentialbenefitsof LAB-derivedpostbiotics for thedevelopmentofnewavenues for therapeutic interventions forAD.