Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells 英文参考文献.docVIP

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Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells 英文参考文献.doc

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Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells 英文参考文献

AmyotrophicLateralSclerosisMultiproteinBiomarkersin PeripheralBloodMononuclearCells GiovanniNardo1,2,SilviaPozzi1,2,MauroPignataro1,2,ElianaLauranzano1,2,GiorgiaSpano1,3 ,Silvia Garbelli4,5,StefaniaMantovani4,5,KalliopiMarinou6,LauraPapetti6,MartaMonteforte7,ValterTorri7, LucaParis2,GianfrancoBazzoni2,ChristianLunetta8,MassimoCorbo8,GabrieleMora6 ,Caterina Bendotti3,ValentinaBonetto1,2* 1DulbeccoTelethonInstitute,Milano,Italy,2DepartmentofMolecularBiochemistryandPharmacology,MarioNegriInstituteforPharmacologicalResearch,Milano,Italy, 3DepartmentofNeuroscience,MarioNegriInstituteforPharmacologicalResearch,Milano,Italy,4IstitutoDiRicoveroeCuraaCarattereScientifico(IRCCS)Fondazione SalvatoreMaugeri,Pavia,Italy,5NationalInstituteforOccupationalSafetyandPrevention(ISPESL),ResearchCenterattheIRCCSFondazioneSalvatoreMaugeri,Pavia, Italy,6IRCCSFondazioneSalvatoreMaugeri,Milano,Italy,7DepartmentofOncology,MarioNegriInstituteforPharmacologicalResearch,Milano,Italy,8NEuroMuscular Omnicentre(NEMO),NiguardaCa’GrandaHospital,Milano,Italy Abstract Background: Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostictestandtherapy.Specificmolecularbiomarkersareurgentlyneededtofacilitateclinicalstudiesand speedupthedevelopmentofeffectivetreatments. Methodology/Principal Findings: We used a two-dimensional difference in gel electrophoresis approach to identify in easilyaccessibleclinicalsamples,peripheralbloodmononuclearcells(PBMC),apanelofproteinbiomarkersthatareclosely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthycontrols(98%),andfrompatientswithneurologicaldisordersthatmayresembleALS(91%),betweentwolevelsof