Selective disruption of TLR2-MyD88 interaction inhibits inflammation and attenuates Alzheimer's pathology
Induction of TLR2 activation depends on its association with the adapter protein MyD88. We have found that TLR2 and MyD88 levels are elevated in the hippocampus and cortex of patients with Alzheimer's disease (AD) and in a 5XFAD mouse model of AD. Since there is no specific inhibitor of TLR2, t...
Saved in:
Published in | The Journal of clinical investigation Vol. 128; no. 10; pp. 4297 - 4312 |
---|---|
Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Clinical Investigation
01.10.2018
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Induction of TLR2 activation depends on its association with the adapter protein MyD88. We have found that TLR2 and MyD88 levels are elevated in the hippocampus and cortex of patients with Alzheimer's disease (AD) and in a 5XFAD mouse model of AD. Since there is no specific inhibitor of TLR2, to target induced TLR2 from a therapeutic angle, we engineered a peptide corresponding to the TLR2-interacting domain of MyD88 (TIDM) that binds to the BB loop of only TLR2, and not other TLRs. Interestingly, WT TIDM peptide inhibited microglial activation induced by fibrillar Aβ1-42 and lipoteichoic acid, but not 1-methyl-4-phenylpyridinium, dsRNA, bacterial lipopolysaccharide, flagellin, or CpG DNA. After intranasal administration, WT TIDM peptide reached the hippocampus, reduced hippocampal glial activation, lowered Aβ burden, attenuated neuronal apoptosis, and improved memory and learning in 5XFAD mice. However, WT TIDM peptide was not effective in 5XFAD mice lacking TLR2. In addition to its effects in 5XFAD mice, WT TIDM peptide also suppressed the disease process in mice with experimental allergic encephalomyelitis and collagen-induced arthritis. Therefore, selective targeting of the activated status of 1 component of the innate immune system by WT TIDM peptide may be beneficial in AD as well as other disorders in which TLR2/MyD88 signaling plays a role in disease pathogenesis. |
---|---|
AbstractList | Induction of TLR2 activation depends on its association with the adapter protein MyD88. We have found that TLR2 and MyD88 levels are elevated in the hippocampus and cortex of patients with Alzheimer’s disease (AD) and in a 5XFAD mouse model of AD. Since there is no specific inhibitor of TLR2, to target induced TLR2 from a therapeutic angle, we engineered a peptide corresponding to the TLR2-interacting domain of MyD88 (TIDM) that binds to the BB loop of only TLR2, and not other TLRs. Interestingly, WT TIDM peptide inhibited microglial activation induced by fibrillar Aβ1-42 and lipoteichoic acid, but not 1-methyl-4-phenylpyridinium, dsRNA, bacterial lipopolysaccharide, flagellin, or CpG DNA. After intranasal administration, WT TIDM peptide reached the hippocampus, reduced hippocampal glial activation, lowered Aβ burden, attenuated neuronal apoptosis, and improved memory and learning in 5XFAD mice. However, WT TIDM peptide was not effective in 5XFAD mice lacking TLR2. In addition to its effects in 5XFAD mice, WT TIDM peptide also suppressed the disease process in mice with experimental allergic encephalomyelitis and collagen-induced arthritis. Therefore, selective targeting of the activated status of 1 component of the innate immune system by WT TIDM peptide may be beneficial in AD as well as other disorders in which TLR2/MyD88 signaling plays a role in disease pathogenesis. Induction of TLR2 activation depends on its association with the adapter protein MyD88. We have found that TLR2 and MyD88 levels are elevated in the hippocampus and cortex of patients with Alzheimer's disease (AD) and in a 5XFAD mouse model of AD. Since there is no specific inhibitor of TLR2, to target induced TLR2 from a therapeutic angle, we engineered a peptide corresponding to the TLR2-interacting domain of MyD88 (TIDM) that binds to the BB loop of only TLR2, and not other TLRs. Interestingly, WT TIDM peptide inhibited microglial activation induced by fibrillar A[beta]1-42 and lipoteichoic acid, but not 1-methyl-4-phenylpyridinium, dsRNA, bacterial lipopolysaccharide, flagellin, or CpG DNA. After intranasal administration, WT TIDM peptide reached the hippocampus, reduced hippocampal glial activation, lowered A[beta] burden, attenuated neuronal apoptosis, and improved memory and learning in 5XFAD mice. However, WT TIDM peptide was not effective in 5XFAD mice lacking TLR2. In addition to its effects in 5XFAD mice, WT TIDM peptide also suppressed the disease process in mice with experimental allergic encephalomyelitis and collagen-induced arthritis. Therefore, selective targeting of the activated status of 1 component of the innate immune system by WT TIDM peptide may be beneficial in AD as well as other disorders in which TLR2/MyD88 signaling plays a role in disease pathogenesis. Induction of TLR2 activation depends on its association with the adapter protein MyD88. We have found that TLR2 and MyD88 levels are elevated in the hippocampus and cortex of patients with Alzheimer's disease (AD) and in a 5XFAD mouse model of AD. Since there is no specific inhibitor of TLR2, to target induced TLR2 from a therapeutic angle, we engineered a peptide corresponding to the TLR2-interacting domain of MyD88 (TIDM) that binds to the BB loop of only TLR2, and not other TLRs. Interestingly, WT TIDM peptide inhibited microglial activation induced by fibrillar Aß1-42 and lipoteichoic acid, but not 1-methyl-4-phenylpyridinium, dsRNA, bacterial lipopolysaccharide, flagellin, or CpG DNA. After intranasal administration, WT TIDM peptide reached the hippocampus, reduced hippocampal glial activation, lowered Aß burden, attenuated neuronal apoptosis, and improved memory and learning in 5XFAD mice. However, WT TIDM peptide was not effective in 5XFAD mice lacking TLR2. In addition to its effects in 5XFAD mice, WT TIDM peptide also suppressed the disease process in mice with experimental allergic encephalomyelitis and collagen-induced arthritis. Therefore, selective targeting of the activated status of 1 component of the innate immune system by WT TIDM peptide may be beneficial in AD as well as other disorders in which TLR2/MyD88 signaling plays a role in disease pathogenesis. |
Audience | Academic |
Author | Mondal, Susanta Corbett, Grant T Kundu, Madhuchhanda Jana, Malabendu Chandra, Sujyoti Pahan, Kalipada Dasarathi, Sridevi Mufson, Elliott J Luan, Chi-Hao Rangasamy, Suresh B Roy, Avik Bennett, David A Mishra, Rama K |
AuthorAffiliation | 4 High Throughput Analysis Laboratory and Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA 6 Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA 5 Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois, USA 2 Barrow Neurological Institute, Phoenix, Arizona, USA 3 Medicinal and Synthetic Chemistry Core, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois, USA 1 Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA |
AuthorAffiliation_xml | – name: 1 Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA – name: 5 Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois, USA – name: 2 Barrow Neurological Institute, Phoenix, Arizona, USA – name: 6 Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA – name: 3 Medicinal and Synthetic Chemistry Core, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois, USA – name: 4 High Throughput Analysis Laboratory and Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA |
Author_xml | – sequence: 1 givenname: Suresh B surname: Rangasamy fullname: Rangasamy, Suresh B organization: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA – sequence: 2 givenname: Malabendu surname: Jana fullname: Jana, Malabendu organization: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA – sequence: 3 givenname: Avik surname: Roy fullname: Roy, Avik organization: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA – sequence: 4 givenname: Grant T surname: Corbett fullname: Corbett, Grant T organization: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA – sequence: 5 givenname: Madhuchhanda surname: Kundu fullname: Kundu, Madhuchhanda organization: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA – sequence: 6 givenname: Sujyoti surname: Chandra fullname: Chandra, Sujyoti organization: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA – sequence: 7 givenname: Susanta surname: Mondal fullname: Mondal, Susanta organization: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA – sequence: 8 givenname: Sridevi surname: Dasarathi fullname: Dasarathi, Sridevi organization: Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA – sequence: 9 givenname: Elliott J surname: Mufson fullname: Mufson, Elliott J organization: Barrow Neurological Institute, Phoenix, Arizona, USA – sequence: 10 givenname: Rama K surname: Mishra fullname: Mishra, Rama K organization: Medicinal and Synthetic Chemistry Core, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois, USA – sequence: 11 givenname: Chi-Hao surname: Luan fullname: Luan, Chi-Hao organization: High Throughput Analysis Laboratory and Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA – sequence: 12 givenname: David A surname: Bennett fullname: Bennett, David A organization: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA – sequence: 13 givenname: Kalipada surname: Pahan fullname: Pahan, Kalipada organization: Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29990310$$D View this record in MEDLINE/PubMed |
BookMark | eNqNkl1r2zAUhsXoWNNusF8wDIN9XLiTZMuWbgYh-8roKLTdboUqH8cKspRZcln266dkWdeMXAwJJM55zhE673uCjpx3gNBTgs8IqembpTaiolg8QBPCGM85LfgRmmBMSS7qgh-jkxCWGJOyZOUjdEyFELggeILMFVjQ0dxC1pgwjKtovMt8m12fX9L8y_od55lxEQaltxnjOnNjYkiX1qq-V9uock2mYgQ3qgghm9qfHZgehpchW6nYeesX68foYatsgCe78xR9_fD-evYpP7_4OJ9Nz3NdYxHzmoBgQnHNKlqkXSsFjWZEacwAK02ExgqwhhYoZq0QUJZlU1WVrlnDG1qcore_-67Gmz6VgouDsnI1mF4Na-mVkfsZZzq58LeyIiyNZdPg1a7B4L-PEKLsTdBgrXLgxyAprnhRVrgiCX3-D7r04-DS9yQlhNcVLwX7Sy2UBZkG59O7etNUTpNalHJSi0TlB6gFuDR7m-RuTQrv8WcH-LQa6I0-WPB6ryAxEX7EhRpDkPOry_9nL77tsy_usR0oG7vg7bhxRtgHd4PVgw9hgPZOFILlxsfy82y-9XFCn90X8Q78Y9ziF_rA7Fs |
CitedBy_id | crossref_primary_10_4049_jimmunol_2100144 crossref_primary_10_1016_j_jneuroim_2019_03_012 crossref_primary_10_1002_glia_24007 crossref_primary_10_1016_j_ejmech_2018_09_068 crossref_primary_10_1016_j_apsb_2023_05_034 crossref_primary_10_3390_microorganisms12010106 crossref_primary_10_1016_j_expneurol_2020_113279 crossref_primary_10_1186_s12974_020_01738_z crossref_primary_10_1515_nipt_2023_0027 crossref_primary_10_3390_cells12242791 crossref_primary_10_1021_acs_jmedchem_0c01049 crossref_primary_10_1038_s41467_021_25767_1 crossref_primary_10_1002_glia_24285 crossref_primary_10_3389_fncel_2021_652593 crossref_primary_10_3390_brainsci11070861 crossref_primary_10_1016_j_bcp_2022_115292 crossref_primary_10_1007_s12035_023_03632_0 crossref_primary_10_3390_ijms23010192 crossref_primary_10_3390_cells11020259 crossref_primary_10_1007_s11427_022_2276_6 crossref_primary_10_4049_jimmunol_2200279 crossref_primary_10_3390_ijms25115711 crossref_primary_10_1016_j_jpha_2023_05_008 crossref_primary_10_1097_MD_0000000000032100 crossref_primary_10_1172_JCI140869 crossref_primary_10_3390_ijms241512464 crossref_primary_10_1523_JNEUROSCI_2447_21_2023 crossref_primary_10_1186_s12979_021_00236_x crossref_primary_10_3389_fnagi_2021_718426 crossref_primary_10_1016_j_celrep_2022_111058 crossref_primary_10_1007_s11481_020_09979_8 crossref_primary_10_1186_s12974_020_01870_w crossref_primary_10_1016_j_bbi_2023_01_009 crossref_primary_10_1016_j_neuint_2024_105742 crossref_primary_10_1042_BSR20222267 crossref_primary_10_18632_aging_102260 crossref_primary_10_3390_pathogens13070528 crossref_primary_10_1186_s40035_021_00273_y crossref_primary_10_3233_ADR_200191 crossref_primary_10_1016_j_neuropharm_2020_108304 crossref_primary_10_3389_fnins_2021_621446 crossref_primary_10_1016_j_exger_2024_112464 crossref_primary_10_3389_fphar_2022_866574 crossref_primary_10_1021_acsinfecdis_3c00348 crossref_primary_10_1038_s12276_022_00755_7 crossref_primary_10_1002_alz_13678 crossref_primary_10_1038_s41598_020_68299_2 crossref_primary_10_1093_nar_gkz981 crossref_primary_10_3233_ADR_230179 crossref_primary_10_1073_pnas_2000653117 crossref_primary_10_1111_fcp_12861 crossref_primary_10_1128_msystems_00004_22 crossref_primary_10_1111_jnc_14813 crossref_primary_10_1371_journal_pntd_0009304 crossref_primary_10_1055_s_0041_1733960 crossref_primary_10_18632_aging_202684 crossref_primary_10_3390_cells11152365 crossref_primary_10_3390_ijms24032083 crossref_primary_10_2174_1570159X18666200128121920 crossref_primary_10_3390_biomedicines11123232 crossref_primary_10_1007_s11481_021_10028_1 crossref_primary_10_3389_fphar_2019_00840 crossref_primary_10_1080_1744666X_2020_1860757 crossref_primary_10_1002_iub_2510 crossref_primary_10_1186_s40035_023_00394_6 crossref_primary_10_1016_j_jneuroim_2020_577362 crossref_primary_10_1016_j_nbd_2024_106427 crossref_primary_10_1093_glycob_cwaa096 crossref_primary_10_1172_JCI161987 crossref_primary_10_1007_s10753_020_01363_1 crossref_primary_10_1016_j_immuni_2024_03_010 crossref_primary_10_1007_s12035_021_02661_x crossref_primary_10_1007_s12035_021_02626_0 crossref_primary_10_1016_j_bioorg_2021_105043 crossref_primary_10_1177_1721727X221095378 crossref_primary_10_3389_fimmu_2022_863449 crossref_primary_10_1080_01677063_2021_1954641 crossref_primary_10_1186_s12868_022_00699_8 crossref_primary_10_1515_nipt_2023_0014 crossref_primary_10_1038_s41392_023_01486_5 crossref_primary_10_1016_j_coi_2021_05_004 crossref_primary_10_1016_j_cyto_2023_156457 crossref_primary_10_2139_ssrn_3379969 crossref_primary_10_1016_j_celrep_2023_112717 crossref_primary_10_1038_s41380_024_02428_5 crossref_primary_10_1038_s41398_021_01509_1 crossref_primary_10_2174_1574885518666230427100702 crossref_primary_10_1152_physrev_00006_2023 crossref_primary_10_1186_s40035_021_00254_1 crossref_primary_10_1155_2020_8253904 crossref_primary_10_1016_j_brainres_2021_147291 crossref_primary_10_1186_s13024_022_00559_3 crossref_primary_10_53394_akd_981907 crossref_primary_10_1016_j_semcdb_2021_10_002 crossref_primary_10_1021_acschemneuro_0c00084 |
Cites_doi | 10.2174/156720512801322573 10.1038/nchembio.2204 10.1016/S0092-8674(00)80897-1 10.1038/374647a0 10.1007/BF00308809 10.1212/01.wnl.0000219668.47116.e6 10.1007/s11481-012-9377-9 10.1523/JNEUROSCI.1243-10.2010 10.1523/JNEUROSCI.13-04-01676.1993 10.3390/molecules23020295 10.1073/pnas.1504890112 10.1523/JNEUROSCI.1023-16.2016 10.1037/0882-7974.17.2.179 10.1021/bi0518390 10.3233/JAD-150040 10.1371/journal.pone.0051869 10.1016/j.cmet.2015.05.022 10.1038/1565 10.1126/science.1141736 10.1523/JNEUROSCI.2637-10.2010 10.1038/nature02761 10.1007/s11481-011-9286-3 10.1016/j.cell.2005.02.008 10.1146/annurev.neuro.22.1.219 10.3389/fimmu.2012.00079 10.1097/00005072-199603000-00002 10.1016/j.celrep.2013.07.028 10.1073/pnas.092136199 10.1128/IAI.00707-08 10.1016/j.bbr.2014.08.034 10.1038/nri3446 10.1212/01.wnl.0000311269.57716.63 10.1089/ars.2006.8.929 10.1523/JNEUROSCI.2842-14.2015 10.1523/JNEUROSCI.3158-09.2009 10.1084/jem.20051529 10.1016/j.jns.2011.11.032 10.1073/pnas.0704908104 10.1523/JNEUROSCI.1146-08.2008 10.1371/journal.pone.0116566 10.4049/jimmunol.1102624 10.1038/nri3713 10.1038/nri2565 10.1186/1742-2094-8-136 10.1038/nn.3028 10.1021/acs.biochem.6b00518 10.1074/jbc.M706579200 10.1038/nrn3880 10.4049/jimmunol.1101121 10.1016/j.tins.2014.03.001 10.4049/jimmunol.181.10.7254 10.1111/nan.12084 10.1007/s11481-013-9503-3 10.1212/01.WNL.0000152982.47274.9E 10.1523/JNEUROSCI.1202-06.2006 10.1007/s11481-013-9447-7 10.1007/s11010-011-1084-y 10.1007/s12016-013-8402-y |
ContentType | Journal Article |
Copyright | COPYRIGHT 2018 American Society for Clinical Investigation Copyright American Society for Clinical Investigation Oct 2018 Copyright © 2018 Rangasamy et al. 2018 Rangasamy et al. |
Copyright_xml | – notice: COPYRIGHT 2018 American Society for Clinical Investigation – notice: Copyright American Society for Clinical Investigation Oct 2018 – notice: Copyright © 2018 Rangasamy et al. 2018 Rangasamy et al. |
DBID | CGR CUY CVF ECM EIF NPM AAYXX CITATION IOV ISR 3V. 7RV 7X7 7XB 88A 88E 8AO 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BEC BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ HCIFZ K9. KB0 LK8 M0S M1P M7P NAPCQ PQEST PQQKQ PQUKI PRINS S0X 7X8 5PM |
DOI | 10.1172/jci96209 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef Gale In Context: Opposing Viewpoints Gale In Context: Science ProQuest Central (Corporate) Proquest Nursing & Allied Health Source Health & Medical Collection ProQuest Central (purchase pre-March 2016) Biology Database (Alumni Edition) Medical Database (Alumni Edition) ProQuest Pharma Collection ProQuest SciTech Collection ProQuest Natural Science Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central ProQuest Central Essentials Biological Science Collection eLibrary ProQuest Central Natural Science Collection ProQuest One Community College ProQuest Central Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Database (Alumni Edition) ProQuest Biological Science Collection Health & Medical Collection (Alumni Edition) Medical Database Biological Science Database Nursing & Allied Health Premium ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China SIRS Editorial MEDLINE - Academic PubMed Central (Full Participant titles) |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef ProQuest Central Student ProQuest Central Essentials SIRS Editorial elibrary ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest Natural Science Collection ProQuest Pharma Collection ProQuest Central China ProQuest Biology Journals (Alumni Edition) ProQuest Central Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Biological Science Collection ProQuest Medical Library (Alumni) ProQuest Biological Science Collection ProQuest One Academic Eastern Edition ProQuest Nursing & Allied Health Source ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection ProQuest Hospital Collection (Alumni) Nursing & Allied Health Premium ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest Nursing & Allied Health Source (Alumni) ProQuest One Academic ProQuest Central (Alumni) MEDLINE - Academic |
DatabaseTitleList | MEDLINE ProQuest Central Student |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database – sequence: 3 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1558-8238 |
EndPage | 4312 |
ExternalDocumentID | A558228179 10_1172_JCI96209 29990310 |
Genre | Research Support, U.S. Gov't, Non-P.H.S Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
GrantInformation_xml | – fundername: BLRD VA grantid: I01 BX003033 – fundername: NIA NIH HHS grantid: P30 AG010161 – fundername: NIA NIH HHS grantid: RF1 AG015819 – fundername: NIA NIH HHS grantid: R01 AG050431 – fundername: U.S. Army Medical Research and Materiel Command grantid: W81XWH-12-1-0065 – fundername: ; grantid: AG050431 – fundername: Zenith Fellows Award from Alzheimer’s Association grantid: ZEN-17-438829 – fundername: US Department of Veterans Affairs grantid: 1I01BX003033 |
GroupedDBID | --- -~X .55 .XZ 08G 08P 29K 354 36B 3V. 5GY 5RE 5RS 7RV 7X7 88A 88E 8AO 8F7 8FE 8FH 8FI 8FJ 8R4 8R5 AAWTL ABOCM ABPMR ABUWG ACGFO ACIHN ACNCT ACPRK ADBBV AEAQA AENEX AFCHL AFKRA AHMBA ALIPV ALMA_UNASSIGNED_HOLDINGS AOIJS ASPBG AVWKF AZFZN BAWUL BBNVY BCU BEC BENPR BHPHI BKEYQ BLC BPHCQ BVXVI CCPQU CGR CS3 CUY CVF D-I DIK DU5 E3Z EBD EBS ECM EIF EJD EMB EMOBN EX3 F5P FRP FYUFA GROUPED_DOAJ GX1 HCIFZ HMCUK HYE IAO IEA IHR IHW INH INR IOF IOV IPO ISR ITC KQ8 L7B LK8 M0L M1P M5~ M7P NAPCQ NPM OBH OCB ODZKP OFXIZ OGEVE OHH OK1 OVD OVIDX P2P P6G PQQKQ PROAC PSQYO Q2X RPM S0X SJFOW SV3 TEORI TR2 TVE UKHRP VVN W2D WH7 WOQ WOW X7M XSB YFH YHG YKV YOC ZY1 ~H1 AAYXX CITATION ZA5 7XB 8FK AZQEC DWQXO GNUQQ K9. PQEST PQUKI PRINS 7X8 5PM |
ID | FETCH-LOGICAL-c709t-71e959a8c56236237aaedc51ac05e0ac19c0ae0cefe205f99e444d666c75d8d23 |
IEDL.DBID | RPM |
ISSN | 0021-9738 |
IngestDate | Tue Sep 17 21:26:47 EDT 2024 Thu Jul 25 10:09:37 EDT 2024 Thu Oct 10 22:41:20 EDT 2024 Fri Feb 23 00:05:49 EST 2024 Fri Feb 02 04:49:15 EST 2024 Fri Feb 02 04:26:35 EST 2024 Thu Aug 01 19:14:23 EDT 2024 Thu Aug 01 20:36:50 EDT 2024 Tue Aug 20 22:12:05 EDT 2024 Thu Sep 26 17:13:50 EDT 2024 Wed Oct 16 00:51:56 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 10 |
Keywords | Innate immunity Neuroscience Inflammation Alzheimer’s disease Autoimmune diseases |
Language | English |
License | This work is licensed under the Creative Commons Attribution 4.0 International License. |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c709t-71e959a8c56236237aaedc51ac05e0ac19c0ae0cefe205f99e444d666c75d8d23 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Authorship note: SBR, MJ, AR, and GTC contributed equally to this work. |
ORCID | 0000-0003-3606-9686 0000-0001-6048-9598 |
OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159992/ |
PMID | 29990310 |
PQID | 2118768495 |
PQPubID | 42166 |
PageCount | 16 |
ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_6159992 proquest_miscellaneous_2068346061 proquest_journals_2118768495 gale_infotracmisc_A558228179 gale_infotracgeneralonefile_A558228179 gale_infotracacademiconefile_A558228179 gale_incontextgauss_ISR_A558228179 gale_incontextgauss_IOV_A558228179 gale_healthsolutions_A558228179 crossref_primary_10_1172_JCI96209 pubmed_primary_29990310 |
PublicationCentury | 2000 |
PublicationDate | 2018-10-01 |
PublicationDateYYYYMMDD | 2018-10-01 |
PublicationDate_xml | – month: 10 year: 2018 text: 2018-10-01 day: 01 |
PublicationDecade | 2010 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States – name: Ann Arbor |
PublicationTitle | The Journal of clinical investigation |
PublicationTitleAlternate | J Clin Invest |
PublicationYear | 2018 |
Publisher | American Society for Clinical Investigation |
Publisher_xml | – name: American Society for Clinical Investigation |
References | B20 B21 B22 B23 B24 B25 B26 B27 B28 B29 Atri (B43) 2011; 17 Suppl 13 B30 B31 B33 B35 B36 B38 B39 B1 B2 B3 B4 Borrelli (B37) 2018; 23 B5 B6 B7 B8 B9 B40 B41 B42 B44 Yu (B34) 2011; 8 B45 B46 B47 B48 B49 Oliveira-Nascimento (B32) 2012; 3 B50 B51 B52 B53 B10 B54 B11 B55 B12 B56 B13 B57 B14 B58 B15 B59 B16 B17 B18 B19 |
References_xml | – ident: B45 doi: 10.2174/156720512801322573 – ident: B53 doi: 10.1038/nchembio.2204 – ident: B58 doi: 10.1016/S0092-8674(00)80897-1 – volume: 17 Suppl 13 start-page: S346 year: 2011 ident: B43 article-title: Effective pharmacological management of Alzheimer’s disease publication-title: Am J Manag Care contributor: fullname: Atri – ident: B11 doi: 10.1038/374647a0 – ident: B48 doi: 10.1007/BF00308809 – ident: B44 doi: 10.1212/01.wnl.0000219668.47116.e6 – ident: B24 doi: 10.1007/s11481-012-9377-9 – ident: B10 doi: 10.1523/JNEUROSCI.1243-10.2010 – ident: B56 doi: 10.1523/JNEUROSCI.13-04-01676.1993 – volume: 23 issue: 2 year: 2018 ident: B37 article-title: Cell penetrating peptides as molecular carriers for anti-cancer agents publication-title: Molecules doi: 10.3390/molecules23020295 contributor: fullname: Borrelli – ident: B26 doi: 10.1073/pnas.1504890112 – ident: B8 doi: 10.1523/JNEUROSCI.1023-16.2016 – ident: B47 doi: 10.1037/0882-7974.17.2.179 – ident: B36 doi: 10.1021/bi0518390 – ident: B22 doi: 10.3233/JAD-150040 – ident: B54 doi: 10.1371/journal.pone.0051869 – ident: B52 doi: 10.1016/j.cmet.2015.05.022 – ident: B2 doi: 10.1038/1565 – ident: B5 doi: 10.1126/science.1141736 – ident: B19 doi: 10.1523/JNEUROSCI.2637-10.2010 – ident: B14 doi: 10.1038/nature02761 – ident: B51 doi: 10.1007/s11481-011-9286-3 – ident: B1 doi: 10.1016/j.cell.2005.02.008 – ident: B21 doi: 10.1146/annurev.neuro.22.1.219 – volume: 3 year: 2012 ident: B32 article-title: The Role of TLR2 in Infection and Immunity publication-title: Front Immunol doi: 10.3389/fimmu.2012.00079 contributor: fullname: Oliveira-Nascimento – ident: B12 doi: 10.1097/00005072-199603000-00002 – ident: B57 doi: 10.1016/j.celrep.2013.07.028 – ident: B4 doi: 10.1073/pnas.092136199 – ident: B40 doi: 10.1128/IAI.00707-08 – ident: B30 doi: 10.1016/j.bbr.2014.08.034 – ident: B15 doi: 10.1038/nri3446 – ident: B13 doi: 10.1212/01.wnl.0000311269.57716.63 – ident: B25 doi: 10.1089/ars.2006.8.929 – ident: B29 doi: 10.1523/JNEUROSCI.2842-14.2015 – ident: B33 doi: 10.1523/JNEUROSCI.3158-09.2009 – ident: B9 doi: 10.1084/jem.20051529 – ident: B35 doi: 10.1016/j.jns.2011.11.032 – ident: B23 doi: 10.1073/pnas.0704908104 – ident: B39 doi: 10.1523/JNEUROSCI.1146-08.2008 – ident: B55 doi: 10.1371/journal.pone.0116566 – ident: B50 doi: 10.4049/jimmunol.1102624 – ident: B20 doi: 10.1038/nri3713 – ident: B16 doi: 10.1038/nri2565 – volume: 8 year: 2011 ident: B34 article-title: Toll-like receptor 2 -196 to -174 del polymorphism influences the susceptibility of Han Chinese people to Alzheimer’s disease publication-title: J Neuroinflammation doi: 10.1186/1742-2094-8-136 contributor: fullname: Yu – ident: B6 doi: 10.1038/nn.3028 – ident: B38 doi: 10.1021/acs.biochem.6b00518 – ident: B42 doi: 10.1074/jbc.M706579200 – ident: B7 doi: 10.1038/nrn3880 – ident: B18 doi: 10.4049/jimmunol.1101121 – ident: B3 doi: 10.1016/j.tins.2014.03.001 – ident: B17 doi: 10.4049/jimmunol.181.10.7254 – ident: B28 doi: 10.1111/nan.12084 – ident: B59 doi: 10.1007/s11481-013-9503-3 – ident: B46 doi: 10.1212/01.WNL.0000152982.47274.9E – ident: B27 doi: 10.1523/JNEUROSCI.1202-06.2006 – ident: B49 doi: 10.1007/s11481-013-9447-7 – ident: B41 doi: 10.1007/s11010-011-1084-y – ident: B31 doi: 10.1007/s12016-013-8402-y |
SSID | ssj0014454 |
Score | 2.6004326 |
Snippet | Induction of TLR2 activation depends on its association with the adapter protein MyD88. We have found that TLR2 and MyD88 levels are elevated in the... |
SourceID | pubmedcentral proquest gale crossref pubmed |
SourceType | Open Access Repository Aggregation Database Index Database |
StartPage | 4297 |
SubjectTerms | Adapter proteins Alzheimer Disease - drug therapy Alzheimer Disease - genetics Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides Animals Apoptosis Arthritis Biomedical research Care and treatment Cellular signal transduction Cognitive ability Collagen CpG islands Development and progression Disease Models, Animal Double-stranded RNA Experimental allergic encephalomyelitis Female Flagellin Gene expression Genetic aspects Health aspects Hippocampus Hippocampus - metabolism Hippocampus - pathology Humans Immune system Inflammation Inflammation - genetics Inflammation - metabolism Inflammation - pathology Innate immunity Intranasal administration Learning Lipopolysaccharides Lipoteichoic acid Male Memory Mice Mice, Transgenic MyD88 protein Myeloid Differentiation Factor 88 - genetics Myeloid Differentiation Factor 88 - metabolism Neurodegeneration Neurodegenerative diseases Neuronal-glial interactions Pathogenesis Peptides Peptides - pharmacology Religious orders Signal Transduction - drug effects Signal Transduction - genetics TLR2 protein Toll-Like Receptor 2 - genetics Toll-Like Receptor 2 - metabolism Toll-like receptors |
SummonAdditionalLinks | – databaseName: ProQuest Central dbid: BENPR link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1Nb9QwELWglRAXxDcpBQJC9GQ18dqOfUJLadVWtKBti3qLHH90I0HSbjYH-PWME2_YIISQcojkFymZjMfP9vgNQm-540IDk8baJA5TxziWSWGw0D4jQBPHXZfle8oPL-jxJbsMC25NSKtcxcQuUJta-zXyXeLrYnMBfP799Q32VaP87moooXEbbZKU-m3azQ_7p19mwz4CpSzoMKdYZhMR5Gdh1N493juSnPhExLUB6c-wvDYujXMm1wahg_voXmCP8bT_3Q_QLVs9RHdOwv74I1SedWVtIILFpmwWbRcP4trF559mBJ_8-ChE7AUiFv1xBrifl0W5bODGgWv0xxhjVZnYy25WrSei8fTbz7ktv9vFThP7AsbdQvxjdHGwf753iEMxBayzRC5xllrJpBLaEx64MqXgY1iqdMJsonQqdaJsoq2zJGFOSkspNTC50RkzwpDJE7RR1ZV9hmLpDHR7WRjHNTXEFcxqSpR1VHNrUh2h1yuL5te9ZkbezTUykq-sHqFX3tR5f9pz6Gb5lDGgLALCRITedAgvUlH5LJgr1TZNfvT563-AzmYj0E4AuRr-nVbh5AF8jRe_GiHfjZBXvfT334DbIyD0ST1uXnlQHmJCk__2YDDQ0Oyf9Hlula1bwCRcTChMKtMIPe0dbjAhEAfphVwjlI1ccQB4pfBxS1XOO8VwoK3wMNn692s9R3eBDvZqv-k22lguWvsCKNeyeBn61S-5DC03 priority: 102 providerName: ProQuest |
Title | Selective disruption of TLR2-MyD88 interaction inhibits inflammation and attenuates Alzheimer's pathology |
URI | https://www.ncbi.nlm.nih.gov/pubmed/29990310 https://www.proquest.com/docview/2118768495 https://search.proquest.com/docview/2068346061 https://pubmed.ncbi.nlm.nih.gov/PMC6159992 |
Volume | 128 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Nb9MwGLa2ISEuiO8FRgkIwSmr49hJfCzdpnXQMXUb6i1y_LFGrOnUtAc48Tf4e_wSXjtJtSAOCCmHRH4ixc77mbzvY4TexiZOJUTSgVTYBNSwOOA4V0EqbUWAJCY2rsr3ND6-pCdTNt1CrO2FcUX7Mi_2y-v5flnMXG3lzVz22zqx_tl4CF4Y4hrS30bbSRS1KXrz64BS1lAvhwFPorRhnAVH3T8ZjnhMsGUKBSvMLStmxx39aZRveaVuxeQtF3T0AN1vYkd_UD_jQ7Sly0fo7rj5O_4YfT13m9qA_fJVUS3Xzhr4C-NffJqQYPztIE19Sw-xrJsZ4HxW5MWqghMDglE3MfqiVL4l3SzXNgz1B9ffZ7qY6-WvHz8r325g7D7EP0GXR4cXw-Og2UwhkAnmqyAJNWdcpNIGPHAkQsB0WCgkZhoLGXKJhcZSG00wM5xrSqmC5EYmTKWKRE_RTrko9S7yuVGg9jxXJpZUEZMzLSkR2lAZaxVKD71u1zS7qTkzMpdrJCRrX4GHXtnFzupuz42aZQPGIGRJwUx46I1DWJKK0lbBXIl1VWWjz1_-AXQ-6YDeNyCzgLcnRdN5ALOx5Fcd5LsO8qqm_v4bcK8DBJ2U3eFWhrLGJlQZsTu7xylkpLBAm2F7p61zK_ViDRgcpxGFpDL00LNa5DZL2Iqsh5KOMG4Alim8OwIK5BjDG4V5_t93vkD3IFKsiYDDPbSzWq71S4jGVnkPdHCa9NCdD4enZxO4Ohh97DmN_A370zod |
link.rule.ids | 230,315,733,786,790,891,12083,21416,27955,27956,31752,31753,33777,33778,43343,43838,53825,53827,74100,74657 |
linkProvider | National Library of Medicine |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3fb9MwELZgSMAL4jeBwQJC7Cla4tiJ_YSqwdSOdkhbh_oWJf6xRoJ0NM0D_PXcJW5oEEJIfYjkL1JzOZ-_c87fEfI2sYlQwKQDpUMbMMuTQIaFDoTCigBFbWLbKt-zZHzJThd84TbcaldWuY2JbaDWK4V75EcU-2InAvj8--vvAXaNwq-rroXGTXKLxTFDP08XfcIFuQJ3KsxRINNYOPFZWLOPTo8nMqFYhrizHP0ZlHdWpWHF5M4SdHKf3HPc0R91L_sBuWGqh-T2zH0df0TKi7apDcQvX5f1ummjgb-y_nx6ToPZjw9C-CgPse4OM8D1sizKTQ0XFhyjO8To55X2UXSzapCG-qOvP5em_GbWh7WP7YvbbfjH5PLk4_x4HLhWCoFKQ7kJ0shILnOhkO7AL81zeBge5SrkJsxVJFWYm1AZa2jIrZSGMaYhtVEp10LT-AnZq1aVeUZ8aTVMellomyimqS24UYzmxjKVGB0pj7zeWjS77hQzsjbTSGm2tbpHDtDUWXfWs59k2YhzICwCgoRH3rQIlKiosAbmKm_qOpt8_vIfoIvzAejQgewK3p3K3bkDeBqUvhog3w2QV53w99-A-wMgzEg1HN56UOYiQp399l8wUD-Md2KVW2VWDWDCRMQMUsrII087h-tNCLRBooyrR9KBK_YA1AkfjlTlstULB9IKN9Pn__5bB-TOeD6bZtPJ2acX5C4Qw073N9one5t1Y14C-doUr9oZ9gv43y6- |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1Lb9QwELagSBUXxJuUQgNC9GRt4o2d-IRWLatuaQvqA-0tSvzoRoKk3WwO8OuZSbxhgxBC2kMkf5E24_HM52T8DSHvhBWJAiZNlQ4sjSwXVAa5ponCigDFrLBtle-ZOLqKjud87uqfaldWuY6JbaDWlcJ35COGfbFFAnx-ZF1ZxJfD6YebW4odpPBLq2uncZfcgywZYBuHeN5vvmDfwJ0ic0hlPE6cEC3k79HxwUwKhiWJG6npzwC9kaGG1ZMb6Wj6kDxwPNKfdBP_iNwx5WOyfeq-lD8hxUXb4AZima-Letm0kcGvrH95cs7o6Y_DJPFRKmLZHWyA60WRF6saLiw4SXeg0c9K7aMAZ9kgJfUn334uTPHdLPdrH1sZt6_kn5Kr6cfLgyPq2ipQFQdyRePQSC6zRCH1gV-cZfAwPMxUwE2QqVCqIDOBMtawgFspTRRFGrY5KuY60Wz8jGyVVWleEF9aDQFA5toKFWlmc25UxDJjIyWMDpVH3qwtmt506hlpu-uIWbq2ukf20NRpd-6zX3DphHMgLwkEDI-8bREoV1HixF9nTV2ns89f_wN0cT4A7TuQrWDuVObOIMDToAzWAPl-gLzuRMD_BtwdAGF1quHw2oNSFx3q9Lcvg4H6YbwTK95KUzWACUQyjmB7GXrkeedwvQmBQkiUdPVIPHDFHoCa4cORsli02uFAYOFmtvPvv7VHtmFxpSezs08vyX3giJ0EcLhLtlbLxrwCHrbKX7cL7BcVCDLq |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Selective+disruption+of+TLR2-MyD88+interaction+inhibits+inflammation+and+attenuates+Alzheimer%27s+pathology&rft.jtitle=The+Journal+of+clinical+investigation&rft.au=Rangasamy%2C+Suresh+B&rft.au=Jana%2C+Malabendu&rft.au=Roy%2C+Avik&rft.au=Corbett%2C+Grant+T&rft.date=2018-10-01&rft.pub=American+Society+for+Clinical+Investigation&rft.issn=0021-9738&rft.eissn=1558-8238&rft.volume=128&rft.issue=10&rft.spage=4297&rft_id=info:doi/10.1172%2FJCI96209&rft.externalDocID=A558228179 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0021-9738&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0021-9738&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0021-9738&client=summon |