Alzheimer s Disease and Inflammatory Regulation

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Ἀσκληπιάδης Αγγελόπουλος
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1 ISSN CN / Q http/ /cjbmb bjmu edu cn Chinese Journal of Biochemistry and Molecular Biology ~ 693 DOI /j cnki cjbmb * AD β Aβ tau neurobrillary tangles β tau AD AD -1β -18 Q189 Alzheimers Disease and Inflammatory Regulation ZHAO Dong-YueCHEN Jin-FengCHEN Qi * Southern Biomedical Research Center at Fujian Normal UniversityFuzhou China Abstract Alzheimers disease ADis a devastating neurodegenerative disease characterized by extracellular deposition of amyloid-βaβplaques and intra-cellular accumulation of hyper-phosphorylated tau protein resulting in NFTs neurobrillary tangles The Aβ and tau hypotheses postulated by its hallmark are not sufficient in explaining all the features of AD Currently inflammation and tissue injury caused by inflammasome have attracted extensive attention in the field of pathogenesis AD This review will give a brief introduction regarding how inflammasome is to be activated and assembled as well as its relation to the highly expressed inflammatory moleculeswhich will offer to a new break-through in pathological mechanism and therapeutic targets of AD Key words Alzheimers diseaseinammasomesinterleukin-1βinterleukin-18 Alzheimers diseasead β 4 AD amyloid-βaβ Aβ 5 tau AD neurobrillary tangles AD 4 AD 2050 AD Aβ tau β tau AD AD Republic of China No WKJ-FJ-28 Aβ * Corresponding author Tel Aβ tau AD @ qq com No WKJ-FJ-28 * Tel @ qq com ReceivedOctober AcceptedFebruary Supported by National Health and Family Planning Commission of People

2 PYD ASC ASC Caspase-1 24 APP /PS1 CARD pro-caspase-1 pro- NLRP3 AD 6 AD caspase-1 caspase-1 7 NLRP3 NLRP3 8 AD NLRP3 NLRP3 AD 2 AD AD 9 AD AD AD AD 19 1 IL- 1β IL-6 TNFα α inflammasomes caspase-1 Caspase-1-1β pro-interleukin- 1β -18 pro-interleukin -18-1β IL-1β -18 IL β NLRsNOD1 NOD2 NLRP3 NLRC4 21-1βIL-1β non-nlrs AIM2 RIG-I IFI16 adapter protein caspase recruitment IL-1β IL-1β domain CARD apoptosisassociated speck-like protein containing a CARD КB IL-1β IL-1β NFКB ASC caspase-1 11 MAPK-p38 BACE1 ASC Naip5 APP Aβ 12 IL-1β caspase-1 12 NLRC4 NLRs IL-1β IL-6 IL-18 NO NLRs 3 IL- 1β APP Aβ 22 NACHT domain IL-1β S100B PYD CARD BIP 13 NLRP3 TLR APP 22 IL-1β tau NLRP3 14 MAPK-p38 23 AD PAMPs IL-1β DAMPs tau NLRP3 NACHT domain Aβ ATP PYD ASC-N NLRP2 NLRP2

3 NLRP3 Aβ 26 NLRP3 3 AD 27 NLRC4 IL-1β 28 ASC NLRC4 IL-1β IL-6 TNFα IL-1β IL-1β 28 BACE1 Aβ 29 Liu NLRC4 IL-1β -18 IL-18 ASC NLRC4 IL-18 NLRC4 ASC IL-1 IL-1β 28 AD IL-18 proil-18 NLRC4 ASC NLRC4 IL-18 IL-1β AD IL-1β 30 IL-18 NLRC4 40 AD 31 IL-18 IL-1β mrna APP AD 41 Aβ 42 Aβ 32 AD AD BACE1 Aβ IL tau Ⅱ AD IL-18 APP 46 BACE1 PS1 N- 2 γ 33 AD IL- 18 3GSK-3 IL-1β 5Cdk5 tau BACE1 35 Aβ IL-18 AD Aβ AD IL-18 IL-1β p60 IL-18 IL-1β NLRP3 IL-1β serine palmitoyltransferasespt IL IL-18 IL-1β SPT ATP IL-1β TNFα 29 NLRP2 AD IL-1β IL SPT Aβ 42 tau pannexin1 ATP 49 IL-1β IL IL- AD 1β IL-18

4 β 13Schroder KTschopp J The inflammasomesj Huang TTChong KYOjcius DMet al IL-1β IL-18 AD Cell Mol Med A AD of neurodegeneration J 627 AD References 1Huang YMucke L Alzheimer mechanisms and therapeutic strategies J Cell Alzheimer s Association 2012 Alzheimer s disease facts and figures J Alzheimers Dement Batsch NMittelman M World Alzheimer Report 2012 Overcoming the stigma of dementiam LondonAlzheimers Disease International2012 4Aizenstein HJNebes RDSaxton JAet al Frequent amyloid deposition without significant cognitive impairment among the elderly J Arch Neurol Johnston HBoutin HAllan S Assessing the contribution of inflammation in models of Alzheimers diseasej Biochem Soc Trans Thomas TNadackal TGThomas K Aspirin and non-steroidal anti-inflammatory drugs inhibit amyloid-β aggregation J Neuroreport Sudduth TLSchmitt FANelson PTet al Neuroinflammatory phenotype in early Alzheimers diseasej Neurobiol Aging Hollingworth PHarold DJones L et al Alzheimers disease geneticscurrent knowledge and future challengesj Int J Geriatr Psychiatry Liu LMartin RChan C Palmitate-activated astrocytes via serine palmitoyltransferase increase BACE1 in primary neurons by sphingomyelinasesj Neurobiol Aging Schmidt RLLenz LL Distinct licensing of IL-18 and IL-1β secretion in response to NLRP3 inflammasome activationj PLoS One e Martinon FMayor ATschopp J The inflammasomes 12Minkiewicz JRivero Vaccari JPKeane RW Human astrocytes express a novel NLRP2 inflammasome J Glia Cell2010 Hirsutella sinensis mycelium suppresses interleukin-1β and interleukin-18 secretion by inhibiting both canonical and non-canonical inflammasomes J Sci Rep Salminen AOjala JSuuronen Tet al Amyloid-β oligomers set fire to inflammasomes and induce Alzheimers pathology J J 16Mathew ALindsley TASheridan Aet al Degraded mitochondrial DNA is a newly identified subtype of the damage associated molecular pattern DAMPfamily and possible trigger guardians of the bodyj Annu Rev immunol J Alzheimers Dis Lightfield KLPersson JTrinidad NJet al Differential requirements for NAIP5 in activation of the NLRC4 inflammasome J Infect Immun van de Veerdonk FLNetea MGDinarello CAet al Inflammasome activation and IL-1β and IL-18 processing during infection J Trends Immunol Tansey MGMcCoy MKFrank-Cannon TC Neuroinflammatory mechanisms in Parkinson s disease potential environmental triggerspathwaysand targets for early therapeutic intervention J Exp Neurol Schultzberg MLindberg CAronsson F et al Inflammation in the nervous system- physiological and pathophysiological aspects J Physiol Behav Das SMishra MKGhosh Jet al Japanese Encephalitis Virus infection induces IL-18 and IL-1β in microglia and astrocytes Correlation with in vitro cytokine responsiveness of glial cells and subsequent neuronal death J J Neuroimmunol Li CZhao RGao Ket al Astrocytes implications for neuroinflammatory pathogenesis of Alzheimers diseasej Curr Alzheimer Res Griffin WSLiu LLi Yet al Interleukin-1 mediates Alzheimer and Lewy body pathologies J J Neuroinflammation Kitazawa MCheng DTsukamoto Met al Blocking IL-1 signaling rescues cognitionattenuates tau pathologyand restores neuronal beta-catenin pathway function in an Alzheimers disease model J J Immunol Heneka MTKummer MPStutz A et al NLRP3 is activated in Alzheimer /s disease and contributes to pathology in APP /PS1 mice J Nature De Nardo DLatz E NLRP3 inflammasomes link inflammation and metabolic disease J Trends Immunol Shi JQZhang CCSun XL et al Antimalarial drug artemisinin

5 7 693 extenuates amyloidogenesis and neuroinflammation in APPswe / PS1dE9 transgenic mice via inhibition of nuclear factor κb and NLRP3 inflammasome activation J CNS Neurosci Ther Liu LChan C IPAF inflammasome is involved in interleukin- 1β production from astrocytesinduced by palmitate implications for Alzheimer s DiseaseJ Neurobiol Aging Liu LMartin RKohler Get al Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in neurons mediated by astrocytesj Exp Neurol Mathew ALindsley TASheridan Aet al Degraded mitochondrial DNA is a newly identified subtype of the damage associated molecular pattern DAMPfamily and possible trigger of neurodegeneration J J Alzheimers Dis Yu JTTan LSong JHet al Interleukin-18 promoter polymorphisms and risk of late onset Alzheimers diseasej Brain Res Ojala JAlafuzoff IHerukka SKet al Expression of interleukin-18 is increased in the brains of Alzheimers disease patients J Neurobiol Aging Bossù PCiaramella ASalani F et al Interleukin-18 produced by peripheral blood cells is increased in Alzheimers disease and correlates with cognitive impairmentj Brain Behav Immun Sutinen EMPirttila TAnderson Get al Pro-inflammatory interleukin-18 increases Alzheimers disease-associated amyloidbeta production in human neuron-like cells J J Neuroinflammation Ojala JOSutinen EMSalminen Aet al Interleukin-18 increases expression of kinases involved in tau phosphorylation in SH-SY5Y neuroblastoma cells J J Neuroimmunol Schmidt RLLenz LL Distinct licensing of IL-18 and IL-1β secretion in response to NLRP3 inflammasome activationj PLoS One e Gupta SKnight AGGupta Set al Saturated long-chain fatty acids activate inflammatory signaling in astrocytes J J Neurochem Borges MCVinolo MACrisma ARet al High-fat diet blunts activation of the nuclear factor-κb signaling pathway in lipopolysaccharide-stimulated peritoneal macrophages of Wistar rats J Nutrition Cho HWu MZhang Let al Signaling dynamics of palmitateinduced ER stress responses mediated by ATF4 in HepG2 cells J BMC Syst Biol Luo XYang YShen Tet al Docosahexaenoic acid ameliorates palmitate-induced lipid accumulation and inflammation through repressing NLRC4 inflammasome activation in HepG2 cells J Nutr Metab Lond Julien CTremblay CPhivilay A et al High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model J Neurobiol Aging Maesako MUemura KKubota Met al Environmental enrichment ameliorated high-fat diet-induced Aβ deposition and memory deficit in APP transgenic micej Neurobiol Aging Patil SSheng LMasserang Aet al Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C- terminal fragment of APP in primary cortical neurons J Neurosci Lett Patil SMelrose JChan C Involvement of astroglial ceramide in palmitic acid-induced Alzheimer-like changes in primary neurons J Eur J Neurosci Karmi AIozzo PViljanen Aet al Increased brain fatty acid uptake in metabolic syndrome J Diabetes Di Paolo GKim TW Linking lipids to Alzheimers disease cholesterol and beyondj Nat Rev Neurosci Patil SChan C Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons J Neurosci Lett Qin JBerdyshev EGoya Jet al Neurons and oligodendrocytes recycle sphingosine 1- phosphate to ceramide significance for apoptosis and multiple sclerosis J J Biol Chem Geekiyanage HUpadhye AChan C Inhibition of serine palmitoyltransferase reduces Aβ and tau hyperphosphorylation in a murine modela safe therapeutic strategy for Alzheimer s disease J Neurobiol Aging

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