[No authors listed]
Oligomeric amyloid-β is currently of interest in amyloid-β mediated toxicity and the pathogenesis of Alzheimer's disease. Mapping the amyloid-β interaction partners could help to discover novel pathways in disease pathogenesis. To discover the amyloid-β interaction partners, we applied a protein array with more than 8100 unique recombinantly expressed human proteins. We identified 324 proteins as potential interactors of oligomeric amyloid-β. The Gene Ontology functional analysis of these proteins showed that oligomeric amyloid-β bound to multiple proteins with diverse functions both from extra and intracellular localizations. This undiscriminating binding phenotype indicates that multiple protein interactions mediate the toxicity of the oligomeric amyloid-β. The most highly impacted cellular system was the protein translation machinery. Oligomeric amyloid-β could bind to altogether 24 proteins involved in translation initiation and elongation. The binding of amyloid-β to purified rat hippocampal ribosomes validated the protein array results. More importantly, in vitro translation assays showed that the oligomeric amyloid-β had a concentration dependent inhibitory activity on translation. Our results indicate that the inhibited protein synthesis is one of the pathways that can be involved in the amyloid-beta induced neurotoxicity.
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FAM27E3, ADARB1, SYNCRIP, MYBBP1A, RAD51AP1, CAMKK2, CELF2, POLD3, PTTG2, UTP14A, SRSF8, SF3B2, KIF2C, WDR5, KATNA1, KIF3A, AKAP13, DDX20, MRPL3, KLF12, OSBPL11, ZNF641, AEBP2, MTFMT, C16orf78, ZNF684, TCEANC2, HMGB4, C1orf87, C1orf131, KCTD18, SPATA4, CARNMT1, RNF32, CSNK1D, CSNK1E, CMTM2, SYT6, CTNNA1, CTNND1, AIFM3, DNAJB7, OR6B3, ZNF385B, PP2D1, CFAP58, CCDC60, APOBEC3H, DDX10, PRICKLE2, OLFML2A, TCEANC, DNM2, S1PR1, AGO4, EEF1D, DZIP1L, ELK1, TIGD1, ANKS6, SUSD3, ZNF449, EPB41L2, ERCC1, ETV3, OR4D6, PATL1, FES, FGF12, FGF13, ICK, ZNF365, TMCC1, RBM34, TAB2, PHF8, ZC3H3, RTF1, ABCF1, PES1, PHYHD1, GABRA4, C9orf43, RPL36, PNKD, GAPDH, FAM32A, DKFZP434K028, TRAF3IP1, RSL1D1, EHF, AGO1, OR2W1, TRMT2A, RPUSD2, FILIP1, TP53TG5, POLL, GLRB, ZNF740, GPR15, NOB1, NTMT1, CCDC59, GTF2E2, ABT1, SENP1, GNL2, PURG, SERPIND1, HDGF, ST6GALNAC6, HK1, HMGA1, HIST2H2AB, HOXC4, CCDC190, APP, TBC1D26, ING2, WASH2P, KCNN3, ARL4D, LAMC1, LMX1B, C6orf201, MAK, MCM7, MYC, TYMSOS, OPA1, OTX2, HP1BP3, PARD6A, ATP5C1, TBX22, FCF1, THAP4, ZC2HC1A, NUSAP1, CDKL3, CDK17, MRPL35, NOL7, NOP16, PHF7, ZCCHC17, VPS29, PLK1, PLRG1, ADAM22, ATP5O, CSNK1G1, RBM11, FAM64A, DDX49, GRAMD1C, HAUS6, SLC41A3, PINX1, ANKZF1, PPP1R10, LRRC8D, THAP1, MRPS18A, MRM3, GIMAP4, DPY19L2P1, DDX43, PNRC2, GPATCH2L, ARHGAP15, MAPK7, PPAN, ZC3HAV1, PAK6, HMCES, ATXN7L3, BBX, AICDA, PDZD4, GPAM, DDX55, FANCM, PTPN12, RAG1, SENP2, RFX5, AVPI1, RPL3L, RPL11, RPL30, RPL31, RPL41, RPS10, RPS11, RPS16, RPS18, RPS19, RPS26, ROBO3, CPEB1, ZNF574, IQCH, KLC2, PLEKHG2, MRPL34, UPF3A, C8orf33, ZNF747, SNRNP70, SRP19, AURKA, SURF2, TAF6, TCF19, TFPI, TGFBR2, THBS4, TSPYL1, TUBG1, MRPL49, WHSC1, ZNF2, ZNF22, ZNF35, ZSCAN21, ZKSCAN8, KCNAB1, PRR14, DDX54, SECISBP2, C1orf116, DHX58, CCDC28B, C1orf35, RBM42, GPANK1, MRPL24, OCEL1, NEIL1, GTDC1, TTLL7, CLIP4, CARF, ATAT1, CPED1, CCDC33, TRIM46, NUAK2, HIST2H2AA3, HIST2H2AC, HIST1H2BM, TRAPPC9, CDCA7, PCBD2, SGIP1, DNAJC30, UTP23, LLPH, C7orf50, DYRK2, CUL3, SPZ1, LNX1, PSRC1, UTP4, RITA1, LTV1, SERAC1, PPFIBP2, TSLP, KCNK5, SCEL, IL18RAP, IER3, DDX18, EIF2S2, KLC4, TAF1B, THAP3, ZNF622, ZNF486, VCY, SART1, TRIM41, USP2, LMF2, HGS, ALKBH8, DEDD, MTG1, NOLC1, IMP4, KIF3B, NCR1, MYOT, TBPL1, GTPBP1, SOCS5, USP6NL, HDAC4, DLGAP5, CDC20, PUM3
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