ABADDirectlyLinksAβtoMitochondrialToxicityinAlzheimer'sDiseaseJovceW.Lustbader.etalScience304,448(2004):DOl:10.1126/science.1091230ADnonTgNone1.5ABADABAD-DPsDABADRPmAPP1.0mAPPIABAD0.5nonTgTgABAD341034503370TgmAPPTgmAPPIABADMagneticField(Gauss)ROSgenerationinABADand/orAPptransfectedmice(A)andcells(D)
ROS generation in ABAD and/or APP transfected mice (A) and cells (D)
Mitochondrial dysfunction in sporadic and genetic Alzheimer's diseaseSusanne Hauptmann a*, Uta Keil a, Isabel Scherping a, Astrid Bonert aAnne Eckert ab, Walter E. Miller aAgePS1-MutationsAPP-mutationsTrisomie211YChangedAPPprocessing1Oligomeric, intracellular ATauFibrillation/extracellularaggregation-1NeurofibrillarytanglesNeuritic plaquesRespiratory chainv)V?ReducedmitochondrialmembranepotentialPS1-Mutations·ReducedATPproductionAging·EnhancedROSproductionMitochondrialand synapticdysfunctionEnhancedApoptosisFig.1.Mitochondrial dysfunction asan earlycommon pathological pathway ofaging,taupathologyand otherunknownriskfactorsof sporadicADas well asPS1andAPPmutationsingeneticAD.Amyloidprecursorprotein(APP),Presenilin1(PS1),reactiveoxygenspecies(ROS).ExperimentalGerontology41(2006)668-673
Fig. 1. Mitochondrial dysfunction as an early common pathological pathway of aging, tau pathology and other unknown riskfactors of sporadic AD as well as PS1and APP mutations in genetic AD. Amyloid precursor protein (APP), Presenilin 1 (PS1), reactive oxygen species (ROS)
MicroglialVascularabnormalitycellNeuronSignallingABmolecule100ONucleusOligomersMitochondrionTruncatedapoE48ImpairedsynapseAB-degradingenzymea-Synuclein米Tau动AmyloidplaqueApoE4NeurofibrillarytanglesDXY.CN
NervecellMitochondrionMitochondrionFreeradicalsatrixH,0InnasmsmEnergymoleculePackingpowerMitochondria are amongthe small structurescaliedoraanellesthatresidewithinacell.Known as the cells'powerhouses,mito.chondria extract energyfrom fuels such asglucoseinthepresenceotoxygentoproducea molecule called adenosine triphosphate,orATP (green),whichprovides energyforthecell,in theprocess,mitochondria generatepotentiallydanserousfreeradicats (red).Anetwork of fiveprotein complexes (yellow,l-V)called the electron transport chain sits in themitochondrion's.deeplyfoldedinnermembrane,ATPis created at thefast complex (V) within theChain and then passes through a channel (lightblue) in the inner membrane betore diffusingthrough the cuter membrane into the cell,Protein complexes I and Inl leak electrons toaxygen,producing superoxide radicals. Highyreactivemolecules suchas tydrogenperaxidkDnare produced by biochemical reactions in thematrix,Thesefreeradicals move into the cellwhere.they can.wreak.havoc,Accumulationofsuch damage may lead to human diseases,includingParkinson'sandAlzheimer's
TheRoleofAbnormalMitochondrialDynamicsinthePathogenesisofAlzheimer'sDiseaseXinglongWang1,BoSu1,LingZheng2,GeorgePerry1,3,MarkA.Smith1,andXiongweiZhu恭Mitochondria DynamicNeurolitochodnriaMorphcNeuronMitochendria DistributiorelincrllMitochondria DysfunctionSynaptieAbnormalityNeuronal Dysfunetiop