MaltSci 麦伴科研

Appearance

文献精选 > 高引权威"阿尔茨海默病"文献

Neuroinflammation in Alzheimer's disease. ​

文献信息 ​

PMID25792098
期刊The Lancet. Neurology
影响因子45.5
JCR 分区Q1
发表年份2015
被引次数2901
关键词神经炎症, 阿尔茨海默病, 免疫机制, 炎症介质, 风险因素
文献类型Journal Article, Review
ISSN1474-4422
页码388-405
期号14(4)
作者Michael T Heneka, Monica J Carson, Joseph El Khoury, Gary E Landreth, Frederic Brosseron, Douglas L Feinstein, Andreas H Jacobs, Tony Wyss-Coray, Javier Vitorica, Richard M Ransohoff, Karl Herrup, Sally A Frautschy, Bente Finsen, Guy C Brown, Alexei Verkhratsky, Koji Yamanaka, Jari Koistinaho, Eicke Latz, Annett Halle, Gabor C Petzold, Terrence Town, Dave Morgan, Mari L Shinohara, V Hugh Perry, Clive Holmes, Nicolas G Bazan, David J Brooks, Stéphane Hunot, Bertrand Joseph, Nikolaus Deigendesch, Olga Garaschuk, Erik Boddeke, Charles A Dinarello, John C Breitner, Greg M Cole, Douglas T Golenbock, Markus P Kummer

一句话小结 ​

本研究揭示了阿尔茨海默病的发病机制不仅涉及神经元，还与大脑免疫机制的相互作用密切相关，错误折叠的蛋白质激活小胶质细胞和星形胶质细胞的免疫反应，从而加重疾病进展。通过全基因组分析发现，特定基因与胶质细胞对错误折叠蛋白的清除能力相关，这为未来阿尔茨海默病的治疗和预防策略提供了新的研究方向。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

神经炎症 · 阿尔茨海默病 · 免疫机制 · 炎症介质 · 风险因素

摘要 ​

越来越多的证据表明，阿尔茨海默病的发病机制不仅限于神经元部分，还与大脑中的免疫机制存在密切的相互作用。错误折叠和聚集的蛋白质与小胶质细胞和星形胶质细胞上的模式识别受体结合，触发了一种以释放炎性介质为特征的先天免疫反应，这种反应有助于疾病的进展和严重程度。全基因组分析表明，几种增加散发性阿尔茨海默病风险的基因编码调节胶质细胞清除错误折叠蛋白和炎性反应的因子。外部因素，包括系统性炎症和肥胖，可能会干扰大脑的免疫过程，并进一步促进疾病的进展。对风险因素的调节以及针对这些免疫机制的研究，可能为阿尔茨海默病的未来治疗或预防策略提供新的思路。

英文摘要 ​

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

麦伴智能科研服务 ​

智能阅读回答你对文献的任何问题，帮助理解文献中的复杂图表和公式
定位观点定位某个观点在文献中的蛛丝马迹
加入知识库完成数据提取，报告撰写等更多高级知识挖掘功能

主要研究问题 ​

  1. 在阿尔茨海默病中，神经炎症如何影响认知功能的具体机制是什么？
  2. 除了基因因素，哪些环境因素被认为对阿尔茨海默病的神经炎症有重要影响？
  3. 有哪些潜在的免疫调节治疗方法可以用于减缓阿尔茨海默病的进展？
  4. 神经炎症在阿尔茨海默病的不同阶段（早期、中期、晚期）中表现出怎样的变化？
  5. 目前关于神经炎症与阿尔茨海默病之间关系的研究有哪些主要的争议或未解之谜？

核心洞察 ​

研究背景和目的 ​

阿尔茨海默病（AD）的发病机制不仅限于神经元，还涉及大脑中的免疫机制。越来越多的证据表明，错误折叠和聚集的蛋白质通过与小胶质细胞和星形胶质细胞上的模式识别受体结合，触发内源性免疫反应。这一研究旨在探讨免疫反应如何影响阿尔茨海默病的进展及其潜在的治疗策略。

主要方法/材料/实验设计 ​

研究采用了基因组范围分析，以识别与散发性阿尔茨海默病相关的基因。这些基因编码的因子主要调节胶质细胞对错误折叠蛋白质的清除和炎症反应。研究还考虑了外部因素如全身性炎症和肥胖对大脑免疫过程的影响。

技术路线流程图 ​

Mermaid diagram

关键结果和发现 ​

  1. 基因识别：识别出多种与散发性阿尔茨海默病相关的基因，这些基因参与胶质细胞对错误折叠蛋白质的清除和调节炎症反应。
  2. 免疫反应：错误折叠的蛋白质与小胶质细胞和星形胶质细胞的相互作用导致炎症介质的释放，进而促进疾病的进展。
  3. 外部因素影响：全身性炎症和肥胖等外部因素可能会干扰大脑的免疫过程，进一步加重疾病。

主要结论/意义/创新性 ​

本研究强调了阿尔茨海默病发病机制中免疫系统的关键作用，提示通过调节免疫机制和风险因素，可能为阿尔茨海默病的治疗或预防提供新的策略。这一发现为未来的研究方向提供了重要的理论基础，尤其是在免疫治疗方面的潜力。

研究局限性和未来方向 ​

  • 局限性：当前研究主要基于基因组分析，尚缺乏临床试验数据来验证发现的有效性和可行性。
  • 未来方向：
    • 深入研究不同基因在阿尔茨海默病中的具体作用。
    • 开展临床试验，评估调节免疫机制的治疗策略的有效性。
    • 探索更多外部因素对大脑免疫过程的影响，以制定综合预防策略。

参考文献 ​

  1. Inflammasome activation and IL-1β and IL-18 processing during infection. - Frank L van de Veerdonk;Mihai G Netea;Charles A Dinarello;Leo A B Joosten - Trends in immunology (2011)
  2. Alzheimer's disease. - Henry W Querfurth;Frank M LaFerla - The New England journal of medicine (2010)
  3. Heme binding induces dimerization and nitration of truncated β-amyloid peptide Aβ16 under oxidative stress. - Grégory Thiabaud;Silvia Pizzocaro;Ricardo Garcia-Serres;Jean-Marc Latour;Enrico Monzani;Luigi Casella - Angewandte Chemie (International ed. in English) (2013)
  4. Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-gamma agonists modulate immunostimulated processing of amyloid precursor protein through regulation of beta-secretase. - Magdalena Sastre;Ilse Dewachter;Gary E Landreth;Timothy M Willson;Thomas Klockgether;Fred van Leuven;Michael T Heneka - The Journal of neuroscience : the official journal of the Society for Neuroscience (2003)
  5. Rosiglitazone monotherapy in mild-to-moderate Alzheimer's disease: results from a randomized, double-blind, placebo-controlled phase III study. - Michael Gold;Claire Alderton;Marina Zvartau-Hind;Sally Egginton;Ann M Saunders;Michael Irizarry;Suzanne Craft;Gary Landreth;Ulla Linnamägi;Sharon Sawchak - Dementia and geriatric cognitive disorders (2010)
  6. Physiology of microglia. - Helmut Kettenmann;Uwe-Karsten Hanisch;Mami Noda;Alexei Verkhratsky - Physiological reviews (2011)
  7. Immunohistochemical study of the beta-chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer's disease brains. - M Q Xia;S X Qin;L J Wu;C R Mackay;B T Hyman - The American journal of pathology (1998)
  8. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. - Rainer Rupprecht;Vassilios Papadopoulos;Gerhard Rammes;Thomas C Baghai;Jinjiang Fan;Nagaraju Akula;Ghislaine Groyer;David Adams;Michael Schumacher - Nature reviews. Drug discovery (2010)
  9. Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease. - Markel Olabarria;Harun N Noristani;Alexei Verkhratsky;José J Rodríguez - Glia (2010)
  10. Body fluid cytokine levels in mild cognitive impairment and Alzheimer's disease: a comparative overview. - Frederic Brosseron;Marius Krauthausen;Markus Kummer;Michael T Heneka - Molecular neurobiology (2014)

引用本文的文献 ​

  1. From Molecular Circuit Dysfunction to Disease: Case Studies in Epilepsy, Traumatic Brain Injury, and Alzheimer's Disease. - Chris G Dulla;Douglas A Coulter;Jokubas Ziburkus - The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry (2016)
  2. The choreography of neuroinflammation in Huntington's disease. - Andrea Crotti;Christopher K Glass - Trends in immunology (2015)
  3. Increased Risk of Dementia in Patients With Erectile Dysfunction: A Population-Based, Propensity Score-Matched, Longitudinal Follow-Up Study. - Chun-Ming Yang;Yuan-Chi Shen;Shih-Feng Weng;Jhi-Joung Wang;Kai-Jen Tien - Medicine (2015)
  4. The neuropathology and cerebrovascular mechanisms of dementia. - Limor Raz;Janice Knoefel;Kiran Bhaskar - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2016)
  5. Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD. - Suzanne Elizabeth Schindler;Anne M Fagan - Frontiers in neurology (2015)
  6. Chronic Brain Inflammation: The Neurochemical Basis for Drugs to Reduce Inflammation. - Bevyn Jarrott;Spencer J Williams - Neurochemical research (2016)
  7. Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders. - Hisham Qosa;David S Miller;Piera Pasinelli;Davide Trotti - Brain research (2015)
  8. Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. - Theoharis C Theoharides;Julia M Stewart;Erifili Hatziagelaki;Gerasimos Kolaitis - Frontiers in neuroscience (2015)
  9. Molecular Targets of Cannabidiol in Neurological Disorders. - Clementino Ibeas Bih;Tong Chen;Alistair V W Nunn;Michaël Bazelot;Mark Dallas;Benjamin J Whalley - Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (2015)
  10. Magnesium Lithospermate B Protects Neurons Against Amyloid β (1-42)-Induced Neurotoxicity Through the NF-κB Pathway. - Feng Jiang;Yongqiang Mao;Huixiang Liu;Ping Xu;Li Zhang;Xiaobo Qian;Xiaofeng Sun - Neurochemical research (2015)

... (2891 更多 篇文献)

© 2025 MaltSci 麦伴科研 - 我们用人工智能技术重塑科研