دورية أكاديمية
أعرض في EDS

Pathogenic Role of RAGE in Tau Transmission and Memory Deficits.

التفاصيل البيبلوغرافية
العنوان: Pathogenic Role of RAGE in Tau Transmission and Memory Deficits.
المؤلفون: Kim Y; Interdisciplinary Program in Neuroscience, Seoul National University, Seoul, Republic of Korea; School of the Biological Sciences, Seoul National University, Seoul, Republic of Korea., Park H; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Kim Y; School of the Biological Sciences, Seoul National University, Seoul, Republic of Korea., Kim SH; School of the Biological Sciences, Seoul National University, Seoul, Republic of Korea., Lee JH; Department of Biochemistry, Yonsei University, Seoul, Republic of Korea., Yang H; School of the Biological Sciences, Seoul National University, Seoul, Republic of Korea., Kim SJ; School of the Biological Sciences, Seoul National University, Seoul, Republic of Korea., Li CM; School of the Biological Sciences, Seoul National University, Seoul, Republic of Korea., Lee H; School of the Biological Sciences, Seoul National University, Seoul, Republic of Korea., Na DH; School of the Biological Sciences, Seoul National University, Seoul, Republic of Korea., Moon S; School of the Biological Sciences, Seoul National University, Seoul, Republic of Korea., Shin Y; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Kam TI; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Lee HW; Department of Biochemistry, Yonsei University, Seoul, Republic of Korea., Kim S; Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Gyeonggi-do, Republic of Korea., Song JJ; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Jung YK; Interdisciplinary Program in Neuroscience, Seoul National University, Seoul, Republic of Korea; School of the Biological Sciences, Seoul National University, Seoul, Republic of Korea. Electronic address: ykjung@snu.ac.kr.
المصدر: Biological psychiatry [Biol Psychiatry] 2023 May 01; Vol. 93 (9), pp. 829-841. Date of Electronic Publication: 2022 Oct 29.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0213264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2402 (Electronic) Linking ISSN: 00063223 NLM ISO Abbreviation: Biol Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Publication: New York, NY : Elsevier
Original Publication: New York, Plenum Pub. Corp.
مواضيع طبية MeSH: Alzheimer Disease*/metabolism , Receptor for Advanced Glycation End Products*/metabolism , tau Proteins*/metabolism , Tauopathies*/metabolism, Animals ; Mice ; Brain/metabolism ; Disease Models, Animal ; Memory Disorders/metabolism ; Mice, Transgenic
مستخلص: Background: In tauopathies, brain regions with tau accumulation strongly correlate with clinical symptoms, and spreading of misfolded tau along neural network leads to disease progression. However, the underlying mechanisms by which tau proteins enter neurons during pathological propagation remain unclear.
Methods: To identify membrane receptors responsible for neuronal propagation of tau oligomers, we established a cell-based tau uptake assay and screened complementary DNA expression library. Tau uptake and propagation were analyzed in vitro and in vivo using a microfluidic device and stereotactic injection. The cognitive function of mice was assessed using behavioral tests.
Results: From a genome-wide cell-based functional screening, RAGE (receptor for advanced glycation end products) was isolated to stimulate the cellular uptake of tau oligomers. Rage deficiency reduced neuronal uptake of pathological tau prepared from rTg4510 mouse brains or cerebrospinal fluid from patients with Alzheimer's disease and slowed tau propagation between neurons cultured in a 3-chamber microfluidic device. RAGE levels were increased in the brains of rTg4510 mice and tau oligomer-treated neurons. Rage knockout decreased tau transmission in the brains of nontransgenic mice after injection with Alzheimer's disease patient-derived tau and ameliorated memory loss after injection with GFP-P301L-tau-AAV. Treatment of RAGE antagonist FPS-ZM1 blocked transsynaptic tau propagation and inflammatory responses and alleviated cognitive impairment in rTg4510 mice.
Conclusions: These results suggest that in neurons and microglia, RAGE binds to pathological tau and facilitates neuronal tau pathology progression and behavioral deficits in tauopathies.
(Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Alzheimer’s disease; FPS-ZM1; Memory loss; RAGE; Tau propagation
المشرفين على المادة: 0 (Receptor for Advanced Glycation End Products)
0 (tau Proteins)
تواريخ الأحداث: Date Created: 20230209 Date Completed: 20230414 Latest Revision: 20230422
رمز التحديث: 20240829
DOI: 10.1016/j.biopsych.2022.10.015
PMID: 36759256
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-2402
DOI:10.1016/j.biopsych.2022.10.015