دورية أكاديمية
Precision Mapping of Amyloid-β Binding Reveals Perisynaptic Localization and Spatially Restricted Plasticity Deficits.
العنوان: | Precision Mapping of Amyloid-β Binding Reveals Perisynaptic Localization and Spatially Restricted Plasticity Deficits. |
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المؤلفون: | Actor-Engel HS; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045., Schwartz SL; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045., Crosby KC; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045., Sinnen BL; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045., Prikhodko O; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045., Ramsay HJ; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045., Bourne JN; Electron Microscopy Core, University of Colorado Anschutz Medical Campus, Aurora, CO 80045., Winborn CS; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045., Lucas A; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045., Smith KR; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045., Dell'Acqua ML; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045., Kennedy MJ; Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045 matthew.kennedy@cuanschutz.edu. |
المصدر: | ENeuro [eNeuro] 2021 Dec 17; Vol. 8 (6). Date of Electronic Publication: 2021 Dec 17 (Print Publication: 2021). |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 101647362 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2373-2822 (Electronic) Linking ISSN: 23732822 NLM ISO Abbreviation: eNeuro Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Washington, DC] : Society for Neuroscience, [2014]- |
مواضيع طبية MeSH: | Alzheimer Disease* , Amyloid beta-Peptides*, Humans ; Neuronal Plasticity ; Neurons ; Synapses |
مستخلص: | Secreted amyloid-β (Aβ) peptide forms neurotoxic oligomeric assemblies thought to cause synaptic deficits associated with Alzheimer's disease (AD). Soluble Aβ oligomers (Aβo) directly bind to neurons with high affinity and block plasticity mechanisms related to learning and memory, trigger loss of excitatory synapses and eventually cause cell death. While Aβo toxicity has been intensely investigated, it remains unclear precisely where Aβo initially binds to the surface of neurons and whether sites of binding relate to synaptic deficits. Here, we used a combination of live cell, super-resolution and ultrastructural imaging techniques to investigate the kinetics, reversibility and nanoscale location of Aβo binding. Surprisingly, Aβo does not bind directly at the synaptic cleft as previously thought but, instead, forms distinct nanoscale clusters encircling the postsynaptic membrane with a significant fraction also binding presynaptic axon terminals. Synaptic plasticity deficits were observed at Aβo-bound synapses but not closely neighboring Aβo-free synapses. Thus, perisynaptic Aβo binding triggers spatially restricted signaling mechanisms to disrupt synaptic function. These data provide new insight into the earliest steps of Aβo pathology and lay the groundwork for future studies evaluating potential surface receptor(s) and local signaling mechanisms responsible for Aβo binding and synapse dysfunction. (Copyright © 2021 Actor-Engel et al.) |
References: | Nature. 2009 Mar 19;458(7236):299-304. (PMID: 19295602) Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):4012-7. (PMID: 19228947) Nat Neurosci. 2010 Feb;13(2):190-6. (PMID: 20037574) Biochim Biophys Acta Biomembr. 2018 Sep;1860(9):1741-1764. (PMID: 29709613) Nat Neurosci. 2009 Dec;12(12):1567-76. (PMID: 19935655) Nat Neurosci. 2012 Sep;15(9):1227-35. (PMID: 22820466) Neurochem Int. 2002 Nov;41(5):345-52. (PMID: 12176077) Ann Neurol. 1990 May;27(5):457-64. (PMID: 2360787) Nature. 2009 Feb 26;457(7233):1128-32. (PMID: 19242475) J Neurosci. 2016 Nov 9;36(45):11532-11543. (PMID: 27911757) Ann Neurol. 1991 Oct;30(4):572-80. (PMID: 1789684) Cell Calcium. 2011 Mar;49(3):184-90. (PMID: 21349580) J Biol Chem. 2010 Mar 5;285(10):7619-32. (PMID: 20032460) Proc Natl Acad Sci U S A. 1998 May 26;95(11):6448-53. (PMID: 9600986) Nature. 1992 Sep 24;359(6393):325-7. (PMID: 1406936) Curr Protoc Neurosci. 2020 Jun;92(1):e96. (PMID: 32497404) J Alzheimers Dis. 2016 May 30;53(3):787-800. (PMID: 27258414) Neuron. 2010 Jun 10;66(5):739-54. (PMID: 20547131) Sci Rep. 2014 Jan 24;4:3854. (PMID: 24458236) J Neurosci. 2019 Jul 24;39(30):5986-6000. (PMID: 31127002) J Neurosci. 2003 Aug 6;23(18):7183-93. (PMID: 12904479) Neuron. 2014 Oct 22;84(2):399-415. (PMID: 25374361) Nat Med. 2008 Aug;14(8):837-42. (PMID: 18568035) Nature. 2002 Apr 4;416(6880):535-9. (PMID: 11932745) Am J Pathol. 2002 Nov;161(5):1869-79. (PMID: 12414533) Nature. 2004 Jun 17;429(6993):761-6. (PMID: 15190253) Eur J Neurosci. 1996 Jul;8(7):1488-500. (PMID: 8758956) Nat Commun. 2019 Mar 13;10(1):1193. (PMID: 30867420) J Histochem Cytochem. 1995 Mar;43(3):283-92. (PMID: 7532656) Langmuir. 2015 Oct 27;31(42):11549-57. (PMID: 26474149) Nature. 2006 Mar 16;440(7082):352-7. (PMID: 16541076) Neurobiol Dis. 2004 Aug;16(3):527-37. (PMID: 15262264) J Neurosci. 2004 Apr 7;24(14):3592-9. (PMID: 15071107) Cell Rep. 2017 Nov 21;21(8):2134-2146. (PMID: 29166605) J Neurosci. 2001 Oct 15;21(20):7993-8003. (PMID: 11588172) Science. 1992 Oct 2;258(5079):126-9. (PMID: 1439760) Cell. 2010 Apr 30;141(3):524-35. (PMID: 20434989) Bioinformatics. 2014 Aug 15;30(16):2389-90. (PMID: 24771516) Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13081-6. (PMID: 16141335) Angew Chem Int Ed Engl. 2008;47(33):6172-6. (PMID: 18646237) Brain Res. 2003 Feb 14;963(1-2):139-49. (PMID: 12560119) Neuron. 2013 Sep 4;79(5):887-902. (PMID: 24012003) J Neurosci. 2007 Mar 14;27(11):2866-75. (PMID: 17360908) J Neurosci. 2004 Dec 15;24(50):11244-52. (PMID: 15601930) Cell Rep. 2019 Apr 16;27(3):658-665.e4. (PMID: 30995464) J Biol Chem. 2007 Apr 13;282(15):11590-601. (PMID: 17308309) Mol Pharmacol. 2016 May;89(5):552-9. (PMID: 26957206) Nature. 2016 Aug 11;536(7615):210-4. (PMID: 27462810) Neurobiol Dis. 2013 Mar;51:161-7. (PMID: 23149068) J Cell Biol. 2010 May 31;189(5):777-82. (PMID: 20513764) Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10417-22. (PMID: 12925731) J Neurosci. 2004 Nov 10;24(45):10191-200. (PMID: 15537891) J Neurosci. 2007 Jan 24;27(4):796-807. (PMID: 17251419) Opt Express. 2014 Jun 30;22(13):15982-91. (PMID: 24977854) Microsc Res Tech. 2000 Jul 1;50(1):58-65. (PMID: 10871549) Nature. 1995 Feb 9;373(6514):523-7. (PMID: 7845465) Cell Rep. 2019 Mar 19;26(12):3284-3297.e3. (PMID: 30893601) |
معلومات مُعتمدة: | R01 MH119154 United States MH NIMH NIH HHS; R35 NS116879 United States NS NINDS NIH HHS; T32 NS099042 United States NS NINDS NIH HHS; R01 NS110383 United States NS NINDS NIH HHS; T32 GM007635 United States GM NIGMS NIH HHS; T32 AG000279 United States AG NIA NIH HHS; F32 MH123053 United States MH NIMH NIH HHS; R21 AG058005 United States AG NIA NIH HHS; F32 AG071073 United States AG NIA NIH HHS |
فهرسة مساهمة: | Keywords: LTP; amyloid-β; plasticity; postsynaptic density; super-resolution; synapse |
المشرفين على المادة: | 0 (Amyloid beta-Peptides) |
تواريخ الأحداث: | Date Created: 20211118 Date Completed: 20220202 Latest Revision: 20230621 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC8687484 |
DOI: | 10.1523/ENEURO.0416-21.2021 |
PMID: | 34789478 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2373-2822 |
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DOI: | 10.1523/ENEURO.0416-21.2021 |