Exosomes: a novel therapeutic target for Alzheimer's disease?
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摘要
Extracellular exosomes are formed inside the cytoplasm of cells in compartments known as multivesicular bodies. Thus, exosomes contain cytoplasmic content. Multivesicular bodies fuse with the plasma membrane and release exosomes into the extracellular environment. Comprehensive research suggests that exosomes act as both inflammatory intermediaries and critical inducers of oxidative stress to drive progression of Alzheimer's disease. An important role of exosomes in Alzheimer's disease includes the formation of neurofibrillary tangles and beta-amyloid production, clearance, and accumulation. In addition, exosomes are involved in neuroinflammation and oxidative stress, which both act as triggers for beta-amyloid pathogenesis and tau hyperphosphorylation. Further, it has been shown that exosomes are strongly associated with beta-amyloid clearance. Thus, effective measures for regulating exosome metabolism may be novel drug targets for Alzheimer's disease.
Extracellular exosomes are formed inside the cytoplasm of cells in compartments known as multivesicular bodies. Thus, exosomes contain cytoplasmic content. Multivesicular bodies fuse with the plasma membrane and release exosomes into the extracellular environment. Comprehensive research suggests that exosomes act as both inflammatory intermediaries and critical inducers of oxidative stress to drive progression of Alzheimer's disease. An important role of exosomes in Alzheimer's disease includes the formation of neurofibrillary tangles and beta-amyloid production, clearance, and accumulation. In addition, exosomes are involved in neuroinflammation and oxidative stress, which both act as triggers for beta-amyloid pathogenesis and tau hyperphosphorylation. Further, it has been shown that exosomes are strongly associated with beta-amyloid clearance. Thus, effective measures for regulating exosome metabolism may be novel drug targets for Alzheimer's disease.
Extracellular exosomes are formed inside the cytoplasm of cells in compartments known as multivesicular bodies. Thus, exosomes contain cytoplasmic content. Multivesicular bodies fuse with the plasma membrane and release exosomes into the extracellular environment. Comprehensive research suggests that exosomes act as both inflammatory intermediaries and critical inducers of oxidative stress to drive progression of Alzheimer's disease. An important role of exosomes in Alzheimer's disease includes the formation of neurofibrillary tangles and beta-amyloid production, clearance, and accumulation. In addition, exosomes are involved in neuroinflammation and oxidative stress, which both act as triggers for beta-amyloid pathogenesis and tau hyperphosphorylation. Further, it has been shown that exosomes are strongly associated with beta-amyloid clearance. Thus, effective measures for regulating exosome metabolism may be novel drug targets for Alzheimer's disease.
引文
Aboud O,Mrak RE,Boop FA,Griffin WS(2013)Epilepsy:neuroinflammation,neurodegeneration,and APOE genotype.Acta Neuropathol Commun 1:41.
Agostinho P,Pliassova A,Oliveira CR,Cunha RA(2015)Localization and trafficking of amyloid-beta protein precursor and secretases:impact on Alzheimer’s disease.J Alzheimers Dis 45:329-347.
Al-Nedawi K(2014)The yin-yang of microvesicles(exosomes)in cancer biology.Front Oncol 4:172.
Alvarez-Erviti L,Seow Y,Schapira AH,Gardiner C,Sargent IL,Wood MJ,Cooper JM(2011)Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission.Neurobiol Dis 42:360-367.
Arscott WT,Tandle AT,Zhao S,Shabason JE,Gordon IK,Schlaff CD,Zhang G,Tofilon PJ,Camphausen KA(2013)Ionizing radiation and glioblastoma exosomes:implications in tumor biology and cell migration.Transl Oncol 6:638-648.
Beach A,Zhang HG,Ratajczak MZ,Kakar SS(2014)Exosomes:an overview of biogenesis,composition and role in ovarian cancer.J Ovarian Res7:14.
Bonda DJ,Wang X,Lee HG,Smith MA,Perry G,Zhu X(2014)Neuronal failure in Alzheimer’s disease:a view through the oxidative stress looking-glass.Neurosci Bull 30:243-252.
Busche MA,Staufenbiel M,Willem M,Haass C,F?rstl H(2016)Mechanisms of Alzheimer’s disease:Neuronal hyperactivity and hypoactivity as new therapeutic targets.Nervenarzt 87:1163-1174.
Butterworth RF(2011)Hepatic encephalopathy:a central neuroinflammatory disorder?Hepatology 53:1372-1376.
Cacabelos R,Cacabelos P,Torrellas C,Tellado I,Carril JC(2014)Pharmacogenomics of Alzheimer’s disease:novel therapeutic strategies for drug development.Methods Mol Biol 1175:323-556.
Cai Z(2014)Monoamine oxidase inhibitors:promising therapeutic agents for Alzheimer’s disease(Review).Mol Med Rep 9:1533-1541.
Cai Z,Zhao B,Ratka A(2011)Oxidative stress and beta-amyloid protein in Alzheimer’s disease.Neuromolecular Med 13:223-250.
Cai Z,Yan Y,Wang Y(2013a)Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder.Clin Interv Aging 8:1089-1095.
Cai Z,Yan LJ,Ratka A(2013b)Telomere shortening and Alzheimer’s disease.Neuromolecular Med 15:25-48.
Cai Z,Hussain MD,Yan LJ(2014)Microglia,neuroinflammation,and beta-amyloid protein in Alzheimer’s disease.Int J Neurosci 124:307-321.
Cai Z,Zhao B,Li K,Zhang L,Li C,Quazi SH,Tan Y(2012)Mammalian target of rapamycin:a valid therapeutic target through the autophagy pathway for Alzheimer’s disease?J Neurosci Res 90:1105-1118.
Candelario KM,Steindler DA(2014)The role of extracellular vesicles in the progression of neurodegenerative disease and cancer.Trends Mol Med20:368-374.
Chang C,Lang H,Geng N,Wang J,Li N,Wang X(2013)Exosomes of BV-2 cells induced by alpha-synuclein:important mediator of neurodegeneration in PD.Neurosci Lett 548:190-195.
Chang YT,Chang WN,Tsai NW,Huang CC,Kung CT,Su YJ,Lin WC,Cheng BC,Su CM,Chiang YF,Lu CH(2014)The roles of biomarkers of oxidative stress and antioxidant in Alzheimer’s disease:a systematic review.Biomed Res Int 2014:182303.
Chen L,Charrier A,Zhou Y,Chen R,Yu B,Agarwal K,Tsukamoto H,Lee LJ,Paulaitis ME,Brigstock DR(2014)Epigenetic regulation of connective tissue growth factor by Micro RNA-214 delivery in exosomes from mouse or human hepatic stellate cells.Hepatology 59:1118-1129.
Chivet M,Hemming F,Pernet-Gallay K,Fraboulet S,Sadoul R(2012)Emerging role of neuronal exosomes in the central nervous system.Front Physiol 3:145.
Chivet M,Javalet C,Hemming F,Pernet-Gallay K,Laulagnier K,Fraboulet S,Sadoul R(2013)Exosomes as a novel way of interneuronal communication.Biochem Soc Trans 41:241-244.
Cox GM,Kithcart AP,Pitt D,Guan Z,Alexander J,Williams JL,Shawler T,Dagia NM,Popovich PG,Satoskar AR,Whitacre CC(2013)Macrophage migration inhibitory factor potentiates autoimmune-mediated neuroinflammation.J Immunol 191:1043-1054.
de la Torre JC(2010)Alzheimer’s disease is incurable but preventable.JAlzheimers Dis 20:861-870.
de Rivero Vaccari JP,Brand F,3rd,Adamczak S,Lee SW,Perez-Barcena J,Wang MY,Bullock MR,Dietrich WD,Keane RW(2016)Exosome-mediated inflammasome signaling after central nervous system injury.JNeurochem 136 Suppl 1:39-48.
De Gracia DJ,Jamison JT,Szymanski JJ,Lewis MK(2008)Translation arrest and ribonomics in post-ischemic brain:layers and layers of players.J Neurochem 106:2288-2301.
Dinkins MB,Dasgupta S,Wang G,Zhu G,Bieberich E(2014)Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFADmouse model of Alzheimer’s disease.Neurobiol Aging 35:1792-1800.
Eldh M,Ekstr?m K,Valadi H,Sj?strand M,Olsson B,Jern?s M,L?tvall J(2010)Exosomes communicate protective messages during oxidative stress;possible role of exosomal shuttle RNA.PLo S One 5:e15353.
Engel PA(2014)Does metabolic failure at the synapse cause Alzheimer’s disease?Med Hypotheses 83:802-808.
Fernandez-Messina L,Gutierrez-Vazquez C,Rivas-Garcia E,Sanchez-Madrid F,de la Fuente H(2015)Immunomodulatory role of micro RNAs transferred by extracellular vesicles.Biol Cell 107:61-77.
Ferreira ME,de Vasconcelos AS,da Costa Vilhena T,da Silva TL,da Silva Barbosa A,Gomes AR,Dolabela MF,Percario S(2015)Oxidative stress in Alzheimer’s disease:should we keep trying antioxidant therapies?Cell Mol Neurobiol 35:595-614.
Fiandaca MS,Kapogiannis D,Mapstone M,Boxer A,Eitan E,Schwartz JB,Abner EL,Petersen RC,Federoff HJ,Miller BL,Goetzl EJ(2015)Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes:A case-control study.Alzheimers Dement 11:600-607.e1.
Fleury A,Martinez MC,Le Lay S(2014)Extracellular vesicles as therapeutic tools in cardiovascular diseases.Front Immunol 5:370.
Fr?hlich D,Kuo WP,Frühbeis C,Sun JJ,Zehendner CM,Luhmann HJ,Pinto S,Toedling J,Trotter J,Kr?mer-Albers EM(2014)Multifaceted effects of oligodendroglial exosomes on neurons:impact on neuronal firing rate,signal transduction and gene regulation.Philos Trans R Soc Lond B Biol Sci 369:20130510.
Gao W,Liu H,Yuan J,Wu C,Huang D,Ma Y,Zhu J,Ma L,Guo J,Shi H,Zou Y,Ge J(2016)Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF-alpha mediated NF-kappa B pathway.J Cell Mol Med 20:2318-2327.
Gendreau KL,Hall GF(2013)Tangles,toxicity,and Tau secretion in AD-new approaches to a vexing problem.Front Neurol 4:160.
Goetzl EJ,Mustapic M,Kapogiannis D,Eitan E,Lobach IV,Goetzl L,Schwartz JB,Miller BL(2016)Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer’s disease.FASEB J 30:3853-3859.
Goldkorn T,Chung S,Filosto S(2013)Lung cancer and lung injury:the dual role of ceramide.Handb Exp Pharmacol:93-113.
Grey M,Dunning CJ,Gaspar R,Grey C,Brundin P,Sparr E,Linse S(2015)Acceleration of alpha-synuclein aggregation by exosomes.J Biol Chem290:2969-2982.
Gupta A,Pulliam L(2014)Exosomes as mediators of neuroinflammation.JNeuroinflammation 11:68.
Kalani A,Tyagi A,Tyagi N(2014)Exosomes:mediators of neurodegeneration,neuroprotection and therapeutics.Mol Neurobiol 49:590-600.
Kamat PK,Kalani A,Rai S,Swarnkar S,Tota S,Nath C,Tyagi N(2016)Mechanism of oxidative stress and synapse dysfunction in the pathogenesis of Alzheimer’s disease:understanding the therapeutics strategies.Mol Neurobiol 53:648-661.
Kanamaru T,Kamimura N,Yokota T,Iuchi K,Nishimaki K,Takami S,Akashiba H,Shitaka Y,Katsura K,Kimura K,Ohta S(2015)Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer’s disease.Neurosci Lett587:126-131.
Kastelowitz N,Yin H(2014)Exosomes and microvesicles:identification and targeting by particle size and lipid chemical probes.Chem Bio Chem15:923-928.
Katsuda T,Oki K,Ochiya T(2015)Potential application of extracellular vesicles of human adipose tissue-derived mesenchymal stem cells in Alzheimer’s disease therapeutics.Methods Mol Biol 1212:171-181.
Kaur U,Banerjee P,Bir A,Sinha M,Biswas A,Chakrabarti S(2015)Reactive oxygen species,redox signaling and neuroinflammation in Alzheimer’s disease:the NF-kappa B connection.Curr Top Med Chem 15:446-457.
Kerner B(2014)Psychiatric genetics,neurogenetics,and neurodegeneration.Front Genet 5:467.
Kong SM,Chan BK,Park JS,Hill KJ,Aitken JB,Cottle L,Farghaian H,Cole AR,Lay PA,Sue CM,Cooper AA(2014)Parkinson’s disease-linked human PARK9/ATP13A2 maintains zinc homeostasis and promotes alpha-Synuclein externalization via exosomes.Hum Mol Genet 23:2816-2833.
Kore RA,Abraham EC(2014)Inflammatory cytokines,interleukin-1 beta and tumor necrosis factor-alpha,upregulated in glioblastoma multiforme,raise the levels of CRYAB in exosomes secreted by U373 glioma cells.Biochem Biophys Res Commun 453:326-331.
Latta CH,Brothers HM,Wilcock DM(2015)Neuroinflammation in Alzheimer’s disease;A source of heterogeneity and target for personalized therapy.Neuroscience 302:103-111.
Laulagnier K,Motta C,Hamdi S,Roy S,Fauvelle F,Pageaux JF,Kobayashi T,Salles JP,Perret B,Bonnerot C,Record M(2004)Mast cell-and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization.Biochem J 380:161-171.
Liu C,Cui G,Zhu M,Kang X,Guo H(2014)Neuroinflammation in Alzheimer’s disease:chemokines produced by astrocytes and chemokine receptors.Int J Clin Exp Pathol 7:8342-8355.
Liu Z,Li T,Li P,Wei N,Zhao Z,Liang H,Ji X,Chen W,Xue M,Wei J(2015)The ambiguous relationship of oxidative stress,tau hyperphosphorylation,and autophagy dysfunction in Alzheimer’s disease.Oxid Med Cell Longev2015:352723.
Lloret A,Badia MC,Giraldo E,Ermak G,Alonso MD,Pallardo FV,Davies KJ,Vina J(2011)Amyloid-beta toxicity and tau hyperphosphorylation are linked via RCAN1 in Alzheimer’s disease.J Alzheimers dis 27:701-709.
Lozano D,Gonzales-Portillo GS,Acosta S,de la Pena I,Tajiri N,Kaneko Y,Borlongan CV(2015)Neuroinflammatory responses to traumatic brain injury:etiology,clinical consequences,and therapeutic opportunities.Neuropsychiatr Dis Treat 11:97-106.
Luque-Contreras D,Carvajal K,Toral-Rios D,Franco-Bocanegra D,Campos-Pe?a V(2014)Oxidative stress and metabolic syndrome:cause or consequence of Alzheimer’s disease?Oxid Med Cell Longev 2014:497802.
Maddahi A,Edvinsson L(2010)Cerebral ischemia induces microvascular pro-inflammatory cytokine expression via the MEK/ERK pathway.J Neuroinflammation 7:14.
McMillin M,Frampton G,Thompson M,Galindo C,Standeford H,Whittington E,Alpini G,De Morrow S(2014)Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline.J Neuroinflammation 11:121.
Meseure D,Drak Alsibai K,Nicolas A(2014)Pivotal role of pervasive neoplastic and stromal cells reprogramming in circulating tumor cells dissemination and metastatic colonization.Cancer Microenviron 7:95-115.
Millington C,Sonego S,Karunaweera N,Rangel A,Aldrich-Wright JR,Campbell IL,Gyengesi E,Münch G(2014)Chronic neuroinflammation in Alzheimer’s disease:new perspectives on animal models and promising candidate drugs.Biomed Res Int 2014:309129.
Morales I,Guzmán-Martínez L,Cerda-Troncoso C,Farias GA,Maccioni RB(2014)Neuroinflammation in the pathogenesis of Alzheimer’s disease.Arational framework for the search of novel therapeutic approaches.Front Cell Neurosci 8:112.
Mouton-Liger F,Rebillat AS,Gourmaud S,Paquet C,Leguen A,Dumurgier J,Bernadelli P,Taupin V,Pradier L,Rooney T,Hugon J(2015)PKR downregulation prevents neurodegeneration and beta-amyloid production in a thiamine-deficient model.Cell Death Dis 6:e1594.
Ohno H(2006)Overview:membrane traffic in multicellular systems:more than just a housekeeper.J Biochem 139:941-942.
Orack JC,Deleidi M,Pitt D,Mahajan K,Nicholas JA,Boster AL,Racke MK,Comabella M,Watanabe F,Imitola J(2015)Concise review:modeling multiple sclerosis with stem cell biological platforms:toward functional validation of cellular and molecular phenotypes in inflammation-induced neurodegeneration.Stem Cells Transl Med 4:252-260.
Ortega F,Stott J,Visser SA,Bendtsen C(2013)Interplay between alpha-,beta-,and gamma-secretases determines biphasic amyloid-beta protein level in the presence of a gamma-secretase inhibitor.J Biol Chem 288:785-792.
Panza F,Solfrizzi V,Seripa D,Imbimbo BP,Lozupone M,Santamato A,Zecca C,Barulli MR,Bellomo A,Pilotto A,Daniele A,Greco A,Logroscino G(2016)Tau-centric targets and drugs in clinical development for the treatment of Alzheimer’s disease.Biomed Res Int 2016:3245935.
Persson T,Popescu BO,Cedazo-Minguez A(2014)Oxidative stress in Alzheimer’s disease:why did antioxidant therapy fail?Oxid Med Cell Longev2014:427318.
Phillips EC,Croft CL,Kurbatskaya K,O’Neill MJ,Hutton ML,Hanger DP,Garwood CJ,Noble W(2014)Astrocytes and neuroinflammation in Alzheimer’s disease.Biochem Soc Trans 42:1321-1325.
Picon PD,Camozzato AL,Lapporte EA,Picon RV,Moser Filho H,Cerveira MO,Chaves ML(2010)Increasing rational use of cholinesterase inhibitors for Alzheimer’s disease in Brazil:public health strategy combining guideline with peer-review of prescriptions.Int J Technol Assess Health Care 26:205-210.
Pottoo FH,Bhowmik M,Vohora D(2014)Raloxifene protects against seizures and neurodegeneration in a mouse model mimicking epilepsy in postmenopausal woman.Eur J Pharm Sci 65:167-173.
Prado N,Ca?amero M,Villalba M,Rodriguez R,Batanero E(2010)Bystander suppression to unrelated allergen sensitization through intranasal administration of tolerogenic exosomes in mouse.Mol Immunol 47:2148-2151.
Pusic AD,Pusic KM,Clayton BL,Kraig RP(2014)IFNgamma-stimulated dendritic cell exosomes as a potential therapeutic for remyelination.J Neuroimmunol 266:12-23.
Qin J,Xu Q(2014)Functions and application of exosomes.Acta Pol Pharm71:537-543.
Rajendran L,Honsho M,Zahn TR,Keller P,Geiger KD,Verkade P,Simons K(2006)Alzheimer’s disease beta-amyloid peptides are released in association with exosomes.Proc Natl Acad Sci U S A 103:11172-11177.
Rajendran L,Bali J,Barr MM,Court FA,Kramer-Albers EM,Picou F,Raposo G,van der Vos KE,van Niel G,Wang J,Breakefield XO(2014)Emerging roles of extracellular vesicles in the nervous system.J Neurosci 34:15482-15489.
Record M(2014)Intercellular communication by exosomes in placenta:a possible role in cell fusion?Placenta 35:297-302.
Russo I,Bubacco L,Greggio E(2012)Exosomes-associated neurodegeneration and progression of Parkinson’s disease.Am J Neurodegener Dis 1:217-225.
Salido-Guadarrama I,Romero-Cordoba S,Peralta-Zaragoza O,Hidalgo-Miranda A,Rodríguez-Dorantes M(2014)Micro RNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer.Onco Targets Ther 7:1327-1338.
Saman S,Lee NC,Inoyo I,Jin J,Li Z,Doyle T,Mc Kee AC,Hall GF(2014)Proteins recruited to exosomes by tau overexpression implicate novel cellular mechanisms linking tau secretion with Alzheimer’s disease.J Alzheimers Dis 40 Suppl 1:S47-70.
Saman S,Kim W,Raya M,Visnick Y,Miro S,Saman S,Jackson B,Mc Kee AC,Alvarez VE,Lee NC,Hall GF(2012)Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease.J Biol Chem 287:3842-3849.
Santos JR,Gois AM,Mendonca DM,Freire MA(2014)Nutritional status,oxidative stress and dementia:the role of selenium in Alzheimer’s disease.Front Aging Neurosci 6:206.
Schneider A,Simons M(2013)Exosomes:vesicular carriers for intercellular communication in neurodegenerative disorders.Cell Tissue Res 352:33-47.
Seifert HA,Collier LA,Chapman CB,Benkovic SA,Willing AE,Pennypacker KR(2014)Pro-inflammatory interferon gamma signaling is directly associated with stroke induced neurodegeneration.J Neuroimmune Pharmacol9:679-689.
Sharples RA,Vella LJ,Nisbet RM,Naylor R,Perez K,Barnham KJ,Masters CL,Hill AF(2008)Inhibition of gamma-secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes.FASEB J 22:1469-1478.
Shi M,Kovac A,Korff A,Cook TJ,Ginghina C,Bullock KM,Yang L,Stewart T,Zheng D,Aro P,Atik A,Kerr KF,Zabetian CP,Peskind ER,Hu SC,Quinn JF,Galasko DR,Montine TJ,Banks WA,Zhang J(2016)CNS tau efflux via exosomes is likely increased in Parkinson’s disease but not in Alzheimer’s disease.Alzheimers Dement 12:1125-1131.
Sluijter JP,Verhage V,Deddens JC,van den Akker F,Doevendans PA(2014)Microvesicles and exosomes for intracardiac communication.Cardiovasc Res 102:302-311.
Soderberg A,Barral AM,S?derstr?m M,Sander B,Rosén A(2007)Redox-signaling transmitted in trans to neighboring cells by melanoma-derived TNF-containing exosomes.Free Radic Biol Med 43:90-99.
Sun D,Zhuang X,Xiang X,Liu Y,Zhang S,Liu C,Barnes S,Grizzle W,Miller D,Zhang HG(2010)A novel nanoparticle drug delivery system:the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.Mol Ther 18:1606-1614.
Tam JH,Seah C,Pasternak SH(2014)The Amyloid Precursor Protein is rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid.Mol Brain 7:54.
Thery C,Zitvogel L,Amigorena S(2002)Exosomes:composition,biogenesis and function.Nat Rev Immunol 2:569-579.
Tonekaboni SH,Mollamohammadi M(2014)Neurodegeneration with brain iron accumulation:an overview.Iran J Child Neurol 8:1-8.
Tsanova B,Spatrick P,Jacobson A,van Hoof A(2014)The RNA exosome affects iron response and sensitivity to oxidative stress.RNA 20:1057-1067.
Tsunemi T,Hamada K,Krainc D(2014)ATP13A2/PARK9 regulates secretion of exosomes and alpha-synuclein.J Neurosci 34:15281-15287.
Vingtdeux V,Sergeant N,Buee L(2012)Potential contribution of exosomes to the prion-like propagation of lesions in Alzheimer’s disease.Front Physiol3:229.
Vitek MP,Bhattacharya K,Glendening JM,Stopa E,Vlassara H,Bucala R,Manogue K,Cerami A(1994)Advanced glycation end products contribute to amyloidosis in Alzheimer disease.Proc Natl Acad Sci U S A 91:4766-4770.
Vlassov AV,Magdaleno S,Setterquist R,Conrad R(2012)Exosomes:current knowledge of their composition,biological functions,and diagnostic and therapeutic potentials.Biochim Biophys Acta 1820:940-948.
Walberer M,Jantzen SU,Backes H,Rueger MA,Keuters MH,Neumaier B,Hoehn M,Fink GR,Graf R,Schroeter M(2014)In-vivo detection of inflammation and neurodegeneration in the chronic phase after permanent embolic stroke in rats.Brain Res 1581:80-88.
Xin H,Li Y,Chopp M(2014)Exosomes/mi RNAs as mediating cell-based therapy of stroke.Front Cell Neurosci 8:377.
Xin H,Li Y,Cui Y,Yang JJ,Zhang ZG,Chopp M(2013a)Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats.J Cereb Blood Flow Metab 33:1711-1715.
Xin H,Li Y,Liu Z,Wang X,Shang X,Cui Y,Zhang ZG,Chopp M(2013b)Mi R-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles.Stem Cells 31:2737-2746.
Yamaguchi T,Izumi Y,Nakamura Y,Yamazaki T,Shiota M,Sano S,Tanaka M,Osada-Oka M,Shimada K,Miura K,Yoshiyama M,Iwao H(2015)Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction.Int J Cardiol 178:239-246.
Yuyama K,Sun H,Sakai S,Mitsutake S,Okada M,Tahara H,Furukawa J,Fujitani N,Shinohara Y,Igarashi Y(2014)Decreased amyloid-beta pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice.J Biol Chem 289:24488-24498.
Yuyama K,Sun H,Usuki S,Sakai S,Hanamatsu H,Mioka T,Kimura N,Okada M,Tahara H,Furukawa J,Fujitani N,Shinohara Y,Igarashi Y(2015)A potential function for neuronal exosomes:sequestering intracerebral amyloid-beta peptide.FEBS Lett 589:84-88.
Zhang F,Jiang L(2015)Neuroinflammation in Alzheimer’s disease.Neuropsychiatr Dis Treat 11:243-256.
Zhang HG,Grizzle WE(2014)Exosomes:a novel pathway of local and distant intercellular communication that facilitates the growth and metastasis of neoplastic lesions.Am J Pathol 184:28-41.
Zhang Y,Chopp M,Meng Y,Katakowski M,Xin H,Mahmood A,Xiong Y(2015)Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury.J Neurosurg 122:856-867.
Zhou Y,Xu H,Xu W,Wang B,Wu H,Tao Y,Zhang B,Wang M,Mao F,Yan Y,Gao S,Gu H,Zhu W,Qian H(2013)Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro.Stem Cell Res Ther 4:34.
Agostinho P,Pliassova A,Oliveira CR,Cunha RA(2015)Localization and trafficking of amyloid-beta protein precursor and secretases:impact on Alzheimer’s disease.J Alzheimers Dis 45:329-347.
Al-Nedawi K(2014)The yin-yang of microvesicles(exosomes)in cancer biology.Front Oncol 4:172.
Alvarez-Erviti L,Seow Y,Schapira AH,Gardiner C,Sargent IL,Wood MJ,Cooper JM(2011)Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission.Neurobiol Dis 42:360-367.
Arscott WT,Tandle AT,Zhao S,Shabason JE,Gordon IK,Schlaff CD,Zhang G,Tofilon PJ,Camphausen KA(2013)Ionizing radiation and glioblastoma exosomes:implications in tumor biology and cell migration.Transl Oncol 6:638-648.
Beach A,Zhang HG,Ratajczak MZ,Kakar SS(2014)Exosomes:an overview of biogenesis,composition and role in ovarian cancer.J Ovarian Res7:14.
Bonda DJ,Wang X,Lee HG,Smith MA,Perry G,Zhu X(2014)Neuronal failure in Alzheimer’s disease:a view through the oxidative stress looking-glass.Neurosci Bull 30:243-252.
Busche MA,Staufenbiel M,Willem M,Haass C,F?rstl H(2016)Mechanisms of Alzheimer’s disease:Neuronal hyperactivity and hypoactivity as new therapeutic targets.Nervenarzt 87:1163-1174.
Butterworth RF(2011)Hepatic encephalopathy:a central neuroinflammatory disorder?Hepatology 53:1372-1376.
Cacabelos R,Cacabelos P,Torrellas C,Tellado I,Carril JC(2014)Pharmacogenomics of Alzheimer’s disease:novel therapeutic strategies for drug development.Methods Mol Biol 1175:323-556.
Cai Z(2014)Monoamine oxidase inhibitors:promising therapeutic agents for Alzheimer’s disease(Review).Mol Med Rep 9:1533-1541.
Cai Z,Zhao B,Ratka A(2011)Oxidative stress and beta-amyloid protein in Alzheimer’s disease.Neuromolecular Med 13:223-250.
Cai Z,Yan Y,Wang Y(2013a)Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder.Clin Interv Aging 8:1089-1095.
Cai Z,Yan LJ,Ratka A(2013b)Telomere shortening and Alzheimer’s disease.Neuromolecular Med 15:25-48.
Cai Z,Hussain MD,Yan LJ(2014)Microglia,neuroinflammation,and beta-amyloid protein in Alzheimer’s disease.Int J Neurosci 124:307-321.
Cai Z,Zhao B,Li K,Zhang L,Li C,Quazi SH,Tan Y(2012)Mammalian target of rapamycin:a valid therapeutic target through the autophagy pathway for Alzheimer’s disease?J Neurosci Res 90:1105-1118.
Candelario KM,Steindler DA(2014)The role of extracellular vesicles in the progression of neurodegenerative disease and cancer.Trends Mol Med20:368-374.
Chang C,Lang H,Geng N,Wang J,Li N,Wang X(2013)Exosomes of BV-2 cells induced by alpha-synuclein:important mediator of neurodegeneration in PD.Neurosci Lett 548:190-195.
Chang YT,Chang WN,Tsai NW,Huang CC,Kung CT,Su YJ,Lin WC,Cheng BC,Su CM,Chiang YF,Lu CH(2014)The roles of biomarkers of oxidative stress and antioxidant in Alzheimer’s disease:a systematic review.Biomed Res Int 2014:182303.
Chen L,Charrier A,Zhou Y,Chen R,Yu B,Agarwal K,Tsukamoto H,Lee LJ,Paulaitis ME,Brigstock DR(2014)Epigenetic regulation of connective tissue growth factor by Micro RNA-214 delivery in exosomes from mouse or human hepatic stellate cells.Hepatology 59:1118-1129.
Chivet M,Hemming F,Pernet-Gallay K,Fraboulet S,Sadoul R(2012)Emerging role of neuronal exosomes in the central nervous system.Front Physiol 3:145.
Chivet M,Javalet C,Hemming F,Pernet-Gallay K,Laulagnier K,Fraboulet S,Sadoul R(2013)Exosomes as a novel way of interneuronal communication.Biochem Soc Trans 41:241-244.
Cox GM,Kithcart AP,Pitt D,Guan Z,Alexander J,Williams JL,Shawler T,Dagia NM,Popovich PG,Satoskar AR,Whitacre CC(2013)Macrophage migration inhibitory factor potentiates autoimmune-mediated neuroinflammation.J Immunol 191:1043-1054.
de la Torre JC(2010)Alzheimer’s disease is incurable but preventable.JAlzheimers Dis 20:861-870.
de Rivero Vaccari JP,Brand F,3rd,Adamczak S,Lee SW,Perez-Barcena J,Wang MY,Bullock MR,Dietrich WD,Keane RW(2016)Exosome-mediated inflammasome signaling after central nervous system injury.JNeurochem 136 Suppl 1:39-48.
De Gracia DJ,Jamison JT,Szymanski JJ,Lewis MK(2008)Translation arrest and ribonomics in post-ischemic brain:layers and layers of players.J Neurochem 106:2288-2301.
Dinkins MB,Dasgupta S,Wang G,Zhu G,Bieberich E(2014)Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFADmouse model of Alzheimer’s disease.Neurobiol Aging 35:1792-1800.
Eldh M,Ekstr?m K,Valadi H,Sj?strand M,Olsson B,Jern?s M,L?tvall J(2010)Exosomes communicate protective messages during oxidative stress;possible role of exosomal shuttle RNA.PLo S One 5:e15353.
Engel PA(2014)Does metabolic failure at the synapse cause Alzheimer’s disease?Med Hypotheses 83:802-808.
Fernandez-Messina L,Gutierrez-Vazquez C,Rivas-Garcia E,Sanchez-Madrid F,de la Fuente H(2015)Immunomodulatory role of micro RNAs transferred by extracellular vesicles.Biol Cell 107:61-77.
Ferreira ME,de Vasconcelos AS,da Costa Vilhena T,da Silva TL,da Silva Barbosa A,Gomes AR,Dolabela MF,Percario S(2015)Oxidative stress in Alzheimer’s disease:should we keep trying antioxidant therapies?Cell Mol Neurobiol 35:595-614.
Fiandaca MS,Kapogiannis D,Mapstone M,Boxer A,Eitan E,Schwartz JB,Abner EL,Petersen RC,Federoff HJ,Miller BL,Goetzl EJ(2015)Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes:A case-control study.Alzheimers Dement 11:600-607.e1.
Fleury A,Martinez MC,Le Lay S(2014)Extracellular vesicles as therapeutic tools in cardiovascular diseases.Front Immunol 5:370.
Fr?hlich D,Kuo WP,Frühbeis C,Sun JJ,Zehendner CM,Luhmann HJ,Pinto S,Toedling J,Trotter J,Kr?mer-Albers EM(2014)Multifaceted effects of oligodendroglial exosomes on neurons:impact on neuronal firing rate,signal transduction and gene regulation.Philos Trans R Soc Lond B Biol Sci 369:20130510.
Gao W,Liu H,Yuan J,Wu C,Huang D,Ma Y,Zhu J,Ma L,Guo J,Shi H,Zou Y,Ge J(2016)Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF-alpha mediated NF-kappa B pathway.J Cell Mol Med 20:2318-2327.
Gendreau KL,Hall GF(2013)Tangles,toxicity,and Tau secretion in AD-new approaches to a vexing problem.Front Neurol 4:160.
Goetzl EJ,Mustapic M,Kapogiannis D,Eitan E,Lobach IV,Goetzl L,Schwartz JB,Miller BL(2016)Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer’s disease.FASEB J 30:3853-3859.
Goldkorn T,Chung S,Filosto S(2013)Lung cancer and lung injury:the dual role of ceramide.Handb Exp Pharmacol:93-113.
Grey M,Dunning CJ,Gaspar R,Grey C,Brundin P,Sparr E,Linse S(2015)Acceleration of alpha-synuclein aggregation by exosomes.J Biol Chem290:2969-2982.
Gupta A,Pulliam L(2014)Exosomes as mediators of neuroinflammation.JNeuroinflammation 11:68.
Kalani A,Tyagi A,Tyagi N(2014)Exosomes:mediators of neurodegeneration,neuroprotection and therapeutics.Mol Neurobiol 49:590-600.
Kamat PK,Kalani A,Rai S,Swarnkar S,Tota S,Nath C,Tyagi N(2016)Mechanism of oxidative stress and synapse dysfunction in the pathogenesis of Alzheimer’s disease:understanding the therapeutics strategies.Mol Neurobiol 53:648-661.
Kanamaru T,Kamimura N,Yokota T,Iuchi K,Nishimaki K,Takami S,Akashiba H,Shitaka Y,Katsura K,Kimura K,Ohta S(2015)Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer’s disease.Neurosci Lett587:126-131.
Kastelowitz N,Yin H(2014)Exosomes and microvesicles:identification and targeting by particle size and lipid chemical probes.Chem Bio Chem15:923-928.
Katsuda T,Oki K,Ochiya T(2015)Potential application of extracellular vesicles of human adipose tissue-derived mesenchymal stem cells in Alzheimer’s disease therapeutics.Methods Mol Biol 1212:171-181.
Kaur U,Banerjee P,Bir A,Sinha M,Biswas A,Chakrabarti S(2015)Reactive oxygen species,redox signaling and neuroinflammation in Alzheimer’s disease:the NF-kappa B connection.Curr Top Med Chem 15:446-457.
Kerner B(2014)Psychiatric genetics,neurogenetics,and neurodegeneration.Front Genet 5:467.
Kong SM,Chan BK,Park JS,Hill KJ,Aitken JB,Cottle L,Farghaian H,Cole AR,Lay PA,Sue CM,Cooper AA(2014)Parkinson’s disease-linked human PARK9/ATP13A2 maintains zinc homeostasis and promotes alpha-Synuclein externalization via exosomes.Hum Mol Genet 23:2816-2833.
Kore RA,Abraham EC(2014)Inflammatory cytokines,interleukin-1 beta and tumor necrosis factor-alpha,upregulated in glioblastoma multiforme,raise the levels of CRYAB in exosomes secreted by U373 glioma cells.Biochem Biophys Res Commun 453:326-331.
Latta CH,Brothers HM,Wilcock DM(2015)Neuroinflammation in Alzheimer’s disease;A source of heterogeneity and target for personalized therapy.Neuroscience 302:103-111.
Laulagnier K,Motta C,Hamdi S,Roy S,Fauvelle F,Pageaux JF,Kobayashi T,Salles JP,Perret B,Bonnerot C,Record M(2004)Mast cell-and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization.Biochem J 380:161-171.
Liu C,Cui G,Zhu M,Kang X,Guo H(2014)Neuroinflammation in Alzheimer’s disease:chemokines produced by astrocytes and chemokine receptors.Int J Clin Exp Pathol 7:8342-8355.
Liu Z,Li T,Li P,Wei N,Zhao Z,Liang H,Ji X,Chen W,Xue M,Wei J(2015)The ambiguous relationship of oxidative stress,tau hyperphosphorylation,and autophagy dysfunction in Alzheimer’s disease.Oxid Med Cell Longev2015:352723.
Lloret A,Badia MC,Giraldo E,Ermak G,Alonso MD,Pallardo FV,Davies KJ,Vina J(2011)Amyloid-beta toxicity and tau hyperphosphorylation are linked via RCAN1 in Alzheimer’s disease.J Alzheimers dis 27:701-709.
Lozano D,Gonzales-Portillo GS,Acosta S,de la Pena I,Tajiri N,Kaneko Y,Borlongan CV(2015)Neuroinflammatory responses to traumatic brain injury:etiology,clinical consequences,and therapeutic opportunities.Neuropsychiatr Dis Treat 11:97-106.
Luque-Contreras D,Carvajal K,Toral-Rios D,Franco-Bocanegra D,Campos-Pe?a V(2014)Oxidative stress and metabolic syndrome:cause or consequence of Alzheimer’s disease?Oxid Med Cell Longev 2014:497802.
Maddahi A,Edvinsson L(2010)Cerebral ischemia induces microvascular pro-inflammatory cytokine expression via the MEK/ERK pathway.J Neuroinflammation 7:14.
McMillin M,Frampton G,Thompson M,Galindo C,Standeford H,Whittington E,Alpini G,De Morrow S(2014)Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline.J Neuroinflammation 11:121.
Meseure D,Drak Alsibai K,Nicolas A(2014)Pivotal role of pervasive neoplastic and stromal cells reprogramming in circulating tumor cells dissemination and metastatic colonization.Cancer Microenviron 7:95-115.
Millington C,Sonego S,Karunaweera N,Rangel A,Aldrich-Wright JR,Campbell IL,Gyengesi E,Münch G(2014)Chronic neuroinflammation in Alzheimer’s disease:new perspectives on animal models and promising candidate drugs.Biomed Res Int 2014:309129.
Morales I,Guzmán-Martínez L,Cerda-Troncoso C,Farias GA,Maccioni RB(2014)Neuroinflammation in the pathogenesis of Alzheimer’s disease.Arational framework for the search of novel therapeutic approaches.Front Cell Neurosci 8:112.
Mouton-Liger F,Rebillat AS,Gourmaud S,Paquet C,Leguen A,Dumurgier J,Bernadelli P,Taupin V,Pradier L,Rooney T,Hugon J(2015)PKR downregulation prevents neurodegeneration and beta-amyloid production in a thiamine-deficient model.Cell Death Dis 6:e1594.
Ohno H(2006)Overview:membrane traffic in multicellular systems:more than just a housekeeper.J Biochem 139:941-942.
Orack JC,Deleidi M,Pitt D,Mahajan K,Nicholas JA,Boster AL,Racke MK,Comabella M,Watanabe F,Imitola J(2015)Concise review:modeling multiple sclerosis with stem cell biological platforms:toward functional validation of cellular and molecular phenotypes in inflammation-induced neurodegeneration.Stem Cells Transl Med 4:252-260.
Ortega F,Stott J,Visser SA,Bendtsen C(2013)Interplay between alpha-,beta-,and gamma-secretases determines biphasic amyloid-beta protein level in the presence of a gamma-secretase inhibitor.J Biol Chem 288:785-792.
Panza F,Solfrizzi V,Seripa D,Imbimbo BP,Lozupone M,Santamato A,Zecca C,Barulli MR,Bellomo A,Pilotto A,Daniele A,Greco A,Logroscino G(2016)Tau-centric targets and drugs in clinical development for the treatment of Alzheimer’s disease.Biomed Res Int 2016:3245935.
Persson T,Popescu BO,Cedazo-Minguez A(2014)Oxidative stress in Alzheimer’s disease:why did antioxidant therapy fail?Oxid Med Cell Longev2014:427318.
Phillips EC,Croft CL,Kurbatskaya K,O’Neill MJ,Hutton ML,Hanger DP,Garwood CJ,Noble W(2014)Astrocytes and neuroinflammation in Alzheimer’s disease.Biochem Soc Trans 42:1321-1325.
Picon PD,Camozzato AL,Lapporte EA,Picon RV,Moser Filho H,Cerveira MO,Chaves ML(2010)Increasing rational use of cholinesterase inhibitors for Alzheimer’s disease in Brazil:public health strategy combining guideline with peer-review of prescriptions.Int J Technol Assess Health Care 26:205-210.
Pottoo FH,Bhowmik M,Vohora D(2014)Raloxifene protects against seizures and neurodegeneration in a mouse model mimicking epilepsy in postmenopausal woman.Eur J Pharm Sci 65:167-173.
Prado N,Ca?amero M,Villalba M,Rodriguez R,Batanero E(2010)Bystander suppression to unrelated allergen sensitization through intranasal administration of tolerogenic exosomes in mouse.Mol Immunol 47:2148-2151.
Pusic AD,Pusic KM,Clayton BL,Kraig RP(2014)IFNgamma-stimulated dendritic cell exosomes as a potential therapeutic for remyelination.J Neuroimmunol 266:12-23.
Qin J,Xu Q(2014)Functions and application of exosomes.Acta Pol Pharm71:537-543.
Rajendran L,Honsho M,Zahn TR,Keller P,Geiger KD,Verkade P,Simons K(2006)Alzheimer’s disease beta-amyloid peptides are released in association with exosomes.Proc Natl Acad Sci U S A 103:11172-11177.
Rajendran L,Bali J,Barr MM,Court FA,Kramer-Albers EM,Picou F,Raposo G,van der Vos KE,van Niel G,Wang J,Breakefield XO(2014)Emerging roles of extracellular vesicles in the nervous system.J Neurosci 34:15482-15489.
Record M(2014)Intercellular communication by exosomes in placenta:a possible role in cell fusion?Placenta 35:297-302.
Russo I,Bubacco L,Greggio E(2012)Exosomes-associated neurodegeneration and progression of Parkinson’s disease.Am J Neurodegener Dis 1:217-225.
Salido-Guadarrama I,Romero-Cordoba S,Peralta-Zaragoza O,Hidalgo-Miranda A,Rodríguez-Dorantes M(2014)Micro RNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer.Onco Targets Ther 7:1327-1338.
Saman S,Lee NC,Inoyo I,Jin J,Li Z,Doyle T,Mc Kee AC,Hall GF(2014)Proteins recruited to exosomes by tau overexpression implicate novel cellular mechanisms linking tau secretion with Alzheimer’s disease.J Alzheimers Dis 40 Suppl 1:S47-70.
Saman S,Kim W,Raya M,Visnick Y,Miro S,Saman S,Jackson B,Mc Kee AC,Alvarez VE,Lee NC,Hall GF(2012)Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease.J Biol Chem 287:3842-3849.
Santos JR,Gois AM,Mendonca DM,Freire MA(2014)Nutritional status,oxidative stress and dementia:the role of selenium in Alzheimer’s disease.Front Aging Neurosci 6:206.
Schneider A,Simons M(2013)Exosomes:vesicular carriers for intercellular communication in neurodegenerative disorders.Cell Tissue Res 352:33-47.
Seifert HA,Collier LA,Chapman CB,Benkovic SA,Willing AE,Pennypacker KR(2014)Pro-inflammatory interferon gamma signaling is directly associated with stroke induced neurodegeneration.J Neuroimmune Pharmacol9:679-689.
Sharples RA,Vella LJ,Nisbet RM,Naylor R,Perez K,Barnham KJ,Masters CL,Hill AF(2008)Inhibition of gamma-secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes.FASEB J 22:1469-1478.
Shi M,Kovac A,Korff A,Cook TJ,Ginghina C,Bullock KM,Yang L,Stewart T,Zheng D,Aro P,Atik A,Kerr KF,Zabetian CP,Peskind ER,Hu SC,Quinn JF,Galasko DR,Montine TJ,Banks WA,Zhang J(2016)CNS tau efflux via exosomes is likely increased in Parkinson’s disease but not in Alzheimer’s disease.Alzheimers Dement 12:1125-1131.
Sluijter JP,Verhage V,Deddens JC,van den Akker F,Doevendans PA(2014)Microvesicles and exosomes for intracardiac communication.Cardiovasc Res 102:302-311.
Soderberg A,Barral AM,S?derstr?m M,Sander B,Rosén A(2007)Redox-signaling transmitted in trans to neighboring cells by melanoma-derived TNF-containing exosomes.Free Radic Biol Med 43:90-99.
Sun D,Zhuang X,Xiang X,Liu Y,Zhang S,Liu C,Barnes S,Grizzle W,Miller D,Zhang HG(2010)A novel nanoparticle drug delivery system:the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.Mol Ther 18:1606-1614.
Tam JH,Seah C,Pasternak SH(2014)The Amyloid Precursor Protein is rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid.Mol Brain 7:54.
Thery C,Zitvogel L,Amigorena S(2002)Exosomes:composition,biogenesis and function.Nat Rev Immunol 2:569-579.
Tonekaboni SH,Mollamohammadi M(2014)Neurodegeneration with brain iron accumulation:an overview.Iran J Child Neurol 8:1-8.
Tsanova B,Spatrick P,Jacobson A,van Hoof A(2014)The RNA exosome affects iron response and sensitivity to oxidative stress.RNA 20:1057-1067.
Tsunemi T,Hamada K,Krainc D(2014)ATP13A2/PARK9 regulates secretion of exosomes and alpha-synuclein.J Neurosci 34:15281-15287.
Vingtdeux V,Sergeant N,Buee L(2012)Potential contribution of exosomes to the prion-like propagation of lesions in Alzheimer’s disease.Front Physiol3:229.
Vitek MP,Bhattacharya K,Glendening JM,Stopa E,Vlassara H,Bucala R,Manogue K,Cerami A(1994)Advanced glycation end products contribute to amyloidosis in Alzheimer disease.Proc Natl Acad Sci U S A 91:4766-4770.
Vlassov AV,Magdaleno S,Setterquist R,Conrad R(2012)Exosomes:current knowledge of their composition,biological functions,and diagnostic and therapeutic potentials.Biochim Biophys Acta 1820:940-948.
Walberer M,Jantzen SU,Backes H,Rueger MA,Keuters MH,Neumaier B,Hoehn M,Fink GR,Graf R,Schroeter M(2014)In-vivo detection of inflammation and neurodegeneration in the chronic phase after permanent embolic stroke in rats.Brain Res 1581:80-88.
Xin H,Li Y,Chopp M(2014)Exosomes/mi RNAs as mediating cell-based therapy of stroke.Front Cell Neurosci 8:377.
Xin H,Li Y,Cui Y,Yang JJ,Zhang ZG,Chopp M(2013a)Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats.J Cereb Blood Flow Metab 33:1711-1715.
Xin H,Li Y,Liu Z,Wang X,Shang X,Cui Y,Zhang ZG,Chopp M(2013b)Mi R-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles.Stem Cells 31:2737-2746.
Yamaguchi T,Izumi Y,Nakamura Y,Yamazaki T,Shiota M,Sano S,Tanaka M,Osada-Oka M,Shimada K,Miura K,Yoshiyama M,Iwao H(2015)Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction.Int J Cardiol 178:239-246.
Yuyama K,Sun H,Sakai S,Mitsutake S,Okada M,Tahara H,Furukawa J,Fujitani N,Shinohara Y,Igarashi Y(2014)Decreased amyloid-beta pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice.J Biol Chem 289:24488-24498.
Yuyama K,Sun H,Usuki S,Sakai S,Hanamatsu H,Mioka T,Kimura N,Okada M,Tahara H,Furukawa J,Fujitani N,Shinohara Y,Igarashi Y(2015)A potential function for neuronal exosomes:sequestering intracerebral amyloid-beta peptide.FEBS Lett 589:84-88.
Zhang F,Jiang L(2015)Neuroinflammation in Alzheimer’s disease.Neuropsychiatr Dis Treat 11:243-256.
Zhang HG,Grizzle WE(2014)Exosomes:a novel pathway of local and distant intercellular communication that facilitates the growth and metastasis of neoplastic lesions.Am J Pathol 184:28-41.
Zhang Y,Chopp M,Meng Y,Katakowski M,Xin H,Mahmood A,Xiong Y(2015)Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury.J Neurosurg 122:856-867.
Zhou Y,Xu H,Xu W,Wang B,Wu H,Tao Y,Zhang B,Wang M,Mao F,Yan Y,Gao S,Gu H,Zhu W,Qian H(2013)Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro.Stem Cell Res Ther 4:34.