دورية أكاديمية
أعرض في EDS

Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.

التفاصيل البيبلوغرافية
العنوان: Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.
المؤلفون: Jagadeesan N; Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA, 92618, USA., Roules GC; Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA, 92618, USA., Chandrashekar DV; Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA, 92618, USA., Yang J; Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA, 92618, USA., Kolluru S; Rancho Cucamonga High School, 11801 Lark Dr, Rancho Cucamonga, CA, 91701, USA., Sumbria RK; Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA, 92618, USA. sumbria@chapman.edu.; Department of Neurology, University of California, Irvine, CA, 92697, USA. sumbria@chapman.edu.
المصدر: Journal of translational medicine [J Transl Med] 2024 Mar 18; Vol. 22 (1), pp. 291. Date of Electronic Publication: 2024 Mar 18.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, 2003-
مواضيع طبية MeSH: Alzheimer Disease*/drug therapy , Amyloidosis*/metabolism , Amyloidosis*/pathology , Biological Products*/metabolism, Mice ; Female ; Animals ; Tumor Necrosis Factor-alpha/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Neuroinflammatory Diseases ; Mice, Transgenic ; Brain/pathology ; Hippocampus/metabolism ; Hippocampus/pathology ; Plaque, Amyloid/metabolism ; Plaque, Amyloid/pathology ; Antibodies/metabolism ; Disease Models, Animal
مستخلص: Background: Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer's disease (AD) if these macromolecules can cross the blood-brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD).
Methods: Eight-month-old female 3xTg-AD mice were injected intraperitoneally with saline (n = 11) or TfRMAb-TNFR (3 mg/kg; n = 11) three days per week for 12 weeks. Age-matched wild-type (WT) mice (n = 9) were treated similarly with saline. Brains were processed for immunostaining and high-resolution multiplex NanoString GeoMx spatial proteomics.
Results: We observed regional differences in proteins relevant to Aβ, tau, and neuroinflammation in the hippocampus of 3xTg-AD mice compared with WT mice. From 64 target proteins studied using spatial proteomics, a comparison of the Aβ-plaque bearing vs. plaque-free regions in the 3xTg-AD mice yielded 39 differentially expressed proteins (DEP) largely related to neuroinflammation (39% of DEP) and Aβ and tau pathology combined (31% of DEP). Hippocampal spatial proteomics revealed that the majority of the proteins modulated by TfRMAb-TNFR in the 3xTg-AD mice were relevant to microglial function (⁓ 33%). TfRMAb-TNFR significantly reduced mature Aβ plaques and increased Aβ-associated microglia around larger Aβ deposits in the 3xTg-AD mice. Further, TfRMAb-TNFR increased mature Aβ plaque-associated microglial TREM2 in 3xTg-AD mice.
Conclusion: Overall, despite the low visual Aβ load in the 11-month-old female 3xTg-AD mice, our results highlight region-specific AD-relevant DEP in the hippocampus of these mice. Chronic TfRMAb-TNFR dosing modulated several DEP involved in AD pathology and showed a largely microglia-centric mechanism of action in the 3xTg-AD mice.
(© 2024. The Author(s).)
References: Brain Pathol. 2007 Jan;17(1):91-103. (PMID: 17493043)
Lab Med. 2021 Mar 15;52(2):188-196. (PMID: 32926148)
Pharmaceutics. 2020 Sep 08;12(9):. (PMID: 32911688)
Mol Biol (Mosk). 2021 Sep-Oct;55(5):734-747. (PMID: 34671002)
J Alzheimers Dis. 2021;80(1):41-52. (PMID: 33459720)
Front Aging Neurosci. 2018 Jan 30;10:04. (PMID: 29441009)
J Neuroinflammation. 2021 Dec 31;18(1):312. (PMID: 34972522)
Alzheimers Res Ther. 2020 Mar 2;12(1):21. (PMID: 32122400)
Brain. 2023 Oct 3;146(10):3969-3990. (PMID: 37183523)
J Cell Mol Med. 2008 Apr;12(2):363-73. (PMID: 18266959)
J Neurosci. 2010 Oct 27;30(43):14299-304. (PMID: 20980585)
PLoS One. 2020 Mar 10;15(3):e0229850. (PMID: 32155191)
Neurobiol Dis. 2017 Jul;103:154-162. (PMID: 28416393)
Neurobiol Aging. 2003 Dec;24(8):1063-70. (PMID: 14643377)
Nat Immunol. 2015 Mar;16(3):229-36. (PMID: 25689443)
PLoS One. 2015 Oct 05;10(10):e0137305. (PMID: 26436670)
Aging Cell. 2019 Feb;18(1):e12873. (PMID: 30488653)
Neuron. 2005 Mar 3;45(5):675-88. (PMID: 15748844)
J Neuroinflammation. 2005 Oct 18;2:23. (PMID: 16232318)
Bioeng Bugs. 2010 Jul-Aug;1(4):231-4. (PMID: 21327054)
Korean J Anesthesiol. 2017 Apr;70(2):144-156. (PMID: 28367284)
Am J Pathol. 2006 Jan;168(1):184-94. (PMID: 16400022)
Behav Genet. 2007 Jan;37(1):79-100. (PMID: 17072762)
Recent Pat Inflamm Allergy Drug Discov. 2018;12(1):69-77. (PMID: 29972106)
Ann Neurol. 1981 Nov;10(5):429-36. (PMID: 6171190)
Mol Neurobiol. 2021 Oct;58(10):5239-5252. (PMID: 34275100)
Alzheimers Dement. 2022 Feb;18(2):360-376. (PMID: 34223696)
J Neurosci. 2001 Feb 15;21(4):1179-88. (PMID: 11160388)
Neurobiol Aging. 2001 Nov-Dec;22(6):873-83. (PMID: 11754994)
J Neuroimmune Pharmacol. 2012 Mar;7(1):42-59. (PMID: 21728035)
Acta Neuropathol. 2013 Oct;126(4):479-97. (PMID: 24052108)
Front Neurosci. 2022 Jan 24;15:785276. (PMID: 35140584)
Neurobiol Dis. 2021 Jan;148:105221. (PMID: 33316368)
J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1200-5. (PMID: 12933918)
Neuropsychopharmacology. 2014 Dec;39(13):2949-62. (PMID: 25047746)
J Clin Immunol. 1999 Jul;19(4):223-30. (PMID: 10471976)
J Cell Biol. 2007 Aug 27;178(5):829-41. (PMID: 17724122)
Nat Commun. 2015 Jan 29;6:6176. (PMID: 25630253)
J Biotechnol. 2010 Mar;146(1-2):84-91. (PMID: 20100527)
Mol Neurodegener. 2019 Jun 11;14(1):23. (PMID: 31186026)
Mol Neurobiol. 2022 Dec;59(12):7236-7252. (PMID: 36151369)
J Alzheimers Dis. 2010;21(2):527-42. (PMID: 20555131)
Am J Public Health. 1996 May;86(5):726-8. (PMID: 8629727)
Acta Neuropathol. 2020 Oct;140(4):477-493. (PMID: 32840654)
Mol Neurodegener. 2018 Dec 20;13(1):66. (PMID: 30572908)
Nat Commun. 2019 Aug 21;10(1):3758. (PMID: 31434879)
Cell Rep. 2022 Nov 22;41(8):111686. (PMID: 36417868)
Drug Metab Dispos. 2011 Jan;39(1):71-6. (PMID: 20884844)
Neurobiol Dis. 2023 Feb;177:105991. (PMID: 36623608)
EMBO Mol Med. 2016 Oct 4;8(10):1184-1196. (PMID: 27534871)
Front Aging Neurosci. 2021 Aug 13;13:720214. (PMID: 34483889)
BMC Neurosci. 2008 Aug 12;9:81. (PMID: 18700006)
Mol Neurodegener. 2021 Dec 20;16(1):84. (PMID: 34930382)
Nat Immunol. 2021 May;22(5):586-594. (PMID: 33859405)
Acta Neuropathol Commun. 2022 Feb 14;10(1):23. (PMID: 35164877)
J Neuroinflammation. 2012 May 29;9:106. (PMID: 22642825)
Brain Res. 2010 Aug 12;1348:139-48. (PMID: 20471965)
Cells. 2022 May 24;11(11):. (PMID: 35681418)
J Biol Chem. 2007 Aug 31;282(35):25464-74. (PMID: 17595159)
Ageing Res Rev. 2021 Nov;71:101451. (PMID: 34450351)
JAMA Neurol. 2014 Apr;71(4):505-8. (PMID: 24493463)
J Alzheimers Dis. 2017;60(1):165-181. (PMID: 28826177)
Brain Res. 2011 Jan 12;1368:239-47. (PMID: 20971085)
J Inflamm Res. 2008;1:29-39. (PMID: 22096345)
J Neurochem. 2005 Aug;94(3):703-12. (PMID: 16033420)
J Negat Results Biomed. 2017 Jan 26;16(1):1. (PMID: 28126004)
Int J Mol Sci. 2023 Jul 21;24(14):. (PMID: 37511507)
J Neuroinflammation. 2020 May 6;17(1):151. (PMID: 32375809)
Cell Death Differ. 2020 Oct;27(10):2810-2827. (PMID: 32341448)
Neurobiol Aging. 2004 Jul;25(6):697-711. (PMID: 15165691)
Sci Rep. 2017 Sep 11;7(1):11118. (PMID: 28894284)
Nat Rev Neurol. 2021 Mar;17(3):157-172. (PMID: 33318676)
Neurochem Res. 2003 Feb;28(2):307-18. (PMID: 12608703)
Mol Pharm. 2017 Jul 3;14(7):2340-2349. (PMID: 28514851)
Cell. 2019 Oct 3;179(2):312-339. (PMID: 31564456)
Pharmaceutics. 2022 Oct 16;14(10):. (PMID: 36297637)
Alzheimers Dement. 2020 Feb;16(2):251-261. (PMID: 31668966)
Int J Alzheimers Dis. 2010 Jul 15;2010:. (PMID: 20798886)
Nat Aging. 2023 May;3(5):494-505. (PMID: 37202515)
J Alzheimers Dis. 2015;44(4):1213-29. (PMID: 25697841)
Brain. 2015 Jun;138(Pt 6):1738-55. (PMID: 25833819)
Biol Psychiatry. 2021 Apr 15;89(8):745-756. (PMID: 32223911)
Alzheimers Dement. 2022 Nov;18(11):2099-2116. (PMID: 35076178)
Neurosci Bull. 2019 Dec;35(6):1126-1137. (PMID: 31127445)
J Neuroinflammation. 2018 Apr 24;15(1):121. (PMID: 29690885)
Neuron. 2003 Jul 31;39(3):409-21. (PMID: 12895417)
Neurobiol Dis. 2009 Apr;34(1):163-77. (PMID: 19320056)
Neurobiol Dis. 2022 Jun 1;167:105684. (PMID: 35247551)
معلومات مُعتمدة: R01 AG062840 United States AG NIA NIH HHS; R01AG072896 United States AG NIA NIH HHS; R01AG062840 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: 3xTg; Alzheimer’s disease; Amyloid beta; Biologic TNF-α inhibitor; Spatial proteomics; Tau; Transferrin receptor antibody
المشرفين على المادة: 0 (Tumor Necrosis Factor-alpha)
0 (Amyloid beta-Protein Precursor)
0 (Antibodies)
0 (Biological Products)
تواريخ الأحداث: Date Created: 20240319 Date Completed: 20240320 Latest Revision: 20240807
رمز التحديث: 20240807
مُعرف محوري في PubMed: PMC10946165
DOI: 10.1186/s12967-024-05008-x
PMID: 38500108
قاعدة البيانات: MEDLINE
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