Mitochondrial dysfunction associated disordersJiangang Long,PH.D.Institute of Mitochondrial Biologyand MedicineXIl'AN Jiaotong University
Mitochondrial dysfunction associated disorders Jiangang Long, PH.D. Institute of Mitochondrial Biology and Medicine XI’AN Jiaotong University
MitochondrialdysfunctionassociateddisordersMitochondrial dysfunction-related diseases:a class of diseasesassociated with mitochondrial oxidative damage and energyimpairment, excluding mitochondrial hereditary diseases.Alzheimer'sdisease(AD)Parkinson's disease(PD)Type2diabetes (TD)Age-relatedmaculardegeneration(AMD)
Mitochondrial dysfunction associated disorders Mitochondrial dysfunction-related diseases: a class of diseases associated with mitochondrial oxidative damage and energy impairment, excluding mitochondrial hereditary diseases. ⚫ Alzheimer’s disease (AD) ⚫ Parkinson’s disease (PD) ⚫ Type 2 diabetes (TD) ⚫ Age-related macular degeneration (AMD) ⚫
Alzheimer's disease,AD阿尔茨海默症
Alzheimer’s disease, AD 阿尔茨海默症
Keypoints Discovery and symptoms of AD, incidence(China)Pathological characteristicsAPP and AβMitochondria and ADOxidative damageDynamicchangesMitochondrialnutrients
Key points Discovery and symptoms of AD, incidence (China) Pathological characteristics APP and Aβ Mitochondria and AD ◼ Oxidative damage ◼ Dynamic changes ◼ Mitochondrial nutrients
Alzheimer's Disease（(AD）First described by German psychiatrist andneuropathologist Alois Alzheimer in 1906The most common form of dementiaPatientsshowed progressive cognitive decline,including memory, thinking, analysis and judgmentvisual space.emotional and other obstaclesAlzheimer'sdiseaseisthemostcommonneurodegenerative disease in the elderlyDr.Alzheimer
Alzheimer’s Disease (AD) Dr. Alzheimer • First described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 • The most common form of dementia • Patients showed progressive cognitive decline, including memory, thinking, analysis and judgment, visual space, emotional and other obstacles. • Alzheimer's disease is the most common neurodegenerative disease in the elderly
ProfilesofADRonaldReagan(1911-2004)
Ronald Reagan (1911-2004) Profiles of AD
Profiles of ADEstimated26.6millionpeopleworldwidesufferedfromAlzheimer'sin2006EstimatesofChinesepatients:6million（2005)and10million(2020),accountsfor1/4oftheworld'sADpatients.AEastWest2510020265-7475-8485+55-64AgegroupFig.2.Age-specificprevalenceofAD,westversuseastChinaNeuroepidemiology2006;27:177-187DOI:10.1159/000096131
• Estimated 26.6 million people worldwide suffered from Alzheimer's in 2006 • Estimates of Chinese patients: 6 million (2005) and 10 million (2020), accounts for 1/4 of the world's AD patients. Profiles of AD
Characteristics of ADPathologicalmanifestations:- Beta-amyloidprecipitation in cerebral cortexand hippocampus一neurofibrillarytangles(神经纤维缠绕，主要为磷酸化神经元微管蛋白一tau蛋白） is mainly phosphorylated neuron tubulin-tau protein.Related mutant genes (account for less than 10% AD cases):-amyloidprecursorprotein (APP),-presenilins 1,2-Apoe4- Two locigavereplicated evidence of association:onewithinCLu(alsocalled APOJ), encoding clusterin or apolipoprotein J, on chromosome 8theother withinCR1, encoding the complement component (3b/4b) receptor1, on chromosome 1 (Nature Genetics volume 41, (2009)
• Pathological manifestations: – Beta-amyloid precipitation in cerebral cortex and hippocampus – neurofibrillary tangles(神经纤维缠绕，主要为磷酸化神经元微管蛋白－tau蛋 白）is mainly phosphorylated neuron tubulin-tau protein. • Related mutant genes (account for less than 10% AD cases): – amyloid precursor protein (APP), – presenilins 1, 2 – Apoe4 – Two loci gave replicated evidence of association: one within CLU (also called APOJ), encoding clusterin or apolipoprotein J, on chromosome 8 the other within CR1, encoding the complement component (3b/4b) receptor 1, on chromosome 1 (Nature Genetics volume 41, (2009) Characteristics of AD
CharacteristicsofAD-Aβ plaquesHumanAβplaqueNeuNAβPlaqueMergeAPPmice(F,24m)ByLongJG,unpulished
Characteristics of AD -Ab plaques Ab Plaque NeuN Merge APP mice (F,24m) Human Ab plaque By Long JG, unpulished
CellAPPMembraneMoleculeFromAPPtobetaamyloidCelInteriorAPP:Amyloid precursorproteinOSBeta-AmyloidBeta amyloid:Aβ isproduced by thehydrolysis of beta secretase (BACE)andEnzymes- secretase by beta-amyloid proteinBeta-Amyloidprecursor (APP)toform39-42aminoPlaqueacidfragmentsA家National InstituteonAging+
From APP to beta amyloid APP: Amyloid precursor protein Beta amyloid: Aβ is produced by the hydrolysis of beta secretase (BACE) and g- secretase by beta-amyloid protein precursor (APP) to form 39-42 amino acid fragments