Appearance
Mitochondrial alterations in Alzheimer's disease.
文献信息
| DOI | 10.3233/jad-2006-9204 |
|---|---|
| PMID | 16873959 |
| 期刊 | Journal of Alzheimer's disease : JAD |
| 影响因子 | 3.1 |
| JCR 分区 | Q2 |
| 发表年份 | 2006 |
| 被引次数 | 148 |
| 关键词 | 线粒体功能障碍, 阿尔茨海默病, 神经元毒性, 代谢缺陷, 形态学改变 |
| 文献类型 | Journal Article, Review |
| ISSN | 1387-2877 |
| 页码 | 119-26 |
| 期号 | 9(2) |
| 作者 | Stavros J Baloyannis |
一句话小结
本研究探讨了阿尔茨海默病中线粒体形态变化与神经元代谢缺乏之间的关系，发现阿尔茨海默病患者的神经元中线粒体显著减少，形态变化与突触损伤存在密切关联，提示线粒体功能障碍可能是疾病早期的重要特征。这些发现为理解阿尔茨海默病的病理机制提供了新的视角，并可能为未来治疗干预提供潜在靶点。
在麦伴科研 (maltsci.com) 搜索更多文献
线粒体功能障碍 · 阿尔茨海默病 · 神经元毒性 · 代谢缺陷 · 形态学改变
摘要
线粒体的形态变化可能与阿尔茨海默病及其他神经退行性疾病中神经元的代谢和能量缺乏有关。线粒体功能障碍也是阿尔茨海默病中β肽诱导神经毒性的一个特征。葡萄糖利用的一般变化、氧化应激的增加以及钙离子(Ca²⁺)的失调是阿尔茨海默病大脑中额外的代谢缺陷，这些缺陷可能与线粒体功能的缺陷有关。其结果是线粒体功能障碍的循环加重，导致氧化损伤增加，直到细胞的能量供应降至生存阈值以下。在对阿尔茨海默病中线粒体形态和形态测量的系列研究中，通过电子显微镜观察，我们注意到海马、听觉皮层、额叶皮层、小脑皮层、爬行纤维、丘脑、苍白球、红核和蓝斑的神经元中出现了显著的形态和形态测量变化。这些形态变化包括线粒体脊的显著变化、亲铂材料的积累以及其大小的减少，相较于正常对照组。线粒体的变化在神经元中尤为明显，这些神经元表现出树突棘的丧失和树突分支的缩短。对大量丘脑和红核神经元的超微结构研究显示，线粒体的变化与细胞骨架病理和淀粉样沉积的积累并不共存，尽管这些变化在显示高尔基体囊泡破裂的神经元中尤为突出。形态测量分析表明，阿尔茨海默病中的线粒体显著减少。线粒体异常的部位和程度与突触变化之间的关系暗示了这些特征在阿尔茨海默病中的密切而早期的关联。
英文摘要
Morphological alterations of mitochondria may be related to metabolic and energy deficiency in neurons in Alzheimer's disease and other neurodegenerative disorders. Mitochondrial dysfunction is also a hallmark of beta peptide induced neuronal toxicity in Alzheimer's disease. A general change in glucose utilization, increased oxidative stress, and Ca;{2+} deregulation are additional metabolic defects in the AD brain that may also be associated with defective mitochondrial function the result is a cycle of increased mitochondrial dysfunction causing increased oxidative damage until the cellular energy supply falls below the threshold for cellular survival. In a series of studies on the morphological and morphometric estimation of mitochondria in Alzheimer's disease, by electron microscopy we noticed substantial morphological and morphometric changes in the neurons of the hippocampus, the acoustic cortex, the frontal cortex, the cerebellar cortex, the climbing fibers, the thalamus, the globus pallidus, the red nucleus and the locus coeruleus. The morphological alterations consisted of considerable changes of the mitochondrial cristae, accumulation of osmiophilic material, and decrease of their size, in comparison with the normal controls. Mitochondrial alterations were particularly prominent in neurons, which showed loss of dendritic spines and abbreviation of the dendritic arborization. The ultrastructural study of large number of neurons in the thalamus and the red nucleus revealed that the mitochondrial alterations did not coexist with cytoskeletal pathology and accumulation of amyloid deposits, though they were prominent in neurons, which demonstrated fragmentation of the cisternae of the Golgi apparatus. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer's disease. The relationship between the site and extent of mitochondrial abnormalities and the synaptic alterations suggests an intimate and early association between these features in Alzheimer's disease.
麦伴智能科研服务
主要研究问题
- 阿尔茨海默病中线粒体功能障碍与神经元代谢缺陷之间的具体机制是什么？
- 线粒体形态变化如何影响阿尔茨海默病患者的认知功能？
- 在阿尔茨海默病中，线粒体的形态和功能变化与其他神经退行性疾病相比有什么不同？
- 线粒体损伤是否会导致阿尔茨海默病中神经元突触结构的改变？如果是，机制是什么？
- 有哪些潜在的治疗策略可以针对阿尔茨海默病中的线粒体功能障碍进行干预？
核心洞察
1. 研究背景和目的
阿尔茨海默病（AD）是一种常见的神经退行性疾病，伴随有神经元的代谢和能量缺乏等多种病理变化。线粒体的功能障碍被认为是AD的一个重要特征，可能与β淀粉样肽诱导的神经毒性密切相关。本研究旨在通过电子显微镜对阿尔茨海默病患者的线粒体形态变化进行深入分析，以探讨线粒体功能障碍与神经元损伤之间的关系。
2. 主要方法和发现
研究采用电子显微镜对阿尔茨海默病患者的海马、听觉皮层、额叶皮层、小脑皮层等多个脑区的神经元进行形态和形态计量的观察与分析。结果显示，与正常对照组相比，阿尔茨海默病患者的线粒体在形态和形态计量上均发生了显著变化，包括线粒体嵴的显著改变、亲油性物质的积累以及线粒体大小的减少。此外，线粒体的变化尤其明显出现在那些表现出树突棘丧失和树突分支缩短的神经元中。尽管线粒体的改变在大量神经元中明显存在，但与细胞骨架病理和淀粉样沉积的积累并无共存的情况。
3. 核心结论
研究表明，阿尔茨海默病患者的线粒体形态和功能发生了显著改变，这些改变与突触结构的变化密切相关，提示线粒体的早期异常可能是导致神经元损伤的关键因素之一。线粒体功能障碍可能通过增加氧化应激和钙离子失调等机制进一步加剧神经元的代谢缺陷，形成一个基于线粒体损伤的恶性循环。
4. 研究意义和影响
本研究揭示了线粒体在阿尔茨海默病中的重要作用，为理解该疾病的发病机制提供了新的视角。线粒体的形态和功能变化与神经元的突触改变之间的紧密联系，可能为未来的治疗策略提供靶点。通过针对线粒体的干预措施，可能有望改善AD患者的神经功能或延缓疾病进程，从而为阿尔茨海默病的临床治疗提供新的思路和方法。
引用本文的文献
- Redox reactions of copper complexes formed with different beta-amyloid peptides and their neuropathological [correction of neuropathalogical] relevance. - Dianlu Jiang;Lijie Men;Jianxiu Wang;Yi Zhang;Sara Chickenyen;Yinsheng Wang;Feimeng Zhou - Biochemistry (2007)
- Novel genetic tools reveal Cdk5's major role in Golgi fragmentation in Alzheimer's disease. - Kai-Hui Sun;Yolanda de Pablo;Fabien Vincent;Emmanuel O Johnson;Angela K Chavers;Kavita Shah - Molecular biology of the cell (2008)
- Amyloid, hyperactivity, and metabolism: theoretical comment on Vloeberghs et al. (2008). - Dave Morgan;Marcia N Gordon - Behavioral neuroscience (2008)
- Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. - Gilad Twig;Brigham Hyde;Orian S Shirihai - Biochimica et biophysica acta (2008)
- Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. - Xinglong Wang;Bo Su;Sandra L Siedlak;Paula I Moreira;Hisashi Fujioka;Yang Wang;Gemma Casadesus;Xiongwei Zhu - Proceedings of the National Academy of Sciences of the United States of America (2008)
- Mitochondria, calcium and cell death: a deadly triad in neurodegeneration. - Fulvio Celsi;Paola Pizzo;Marisa Brini;Sara Leo;Carmen Fotino;Paolo Pinton;Rosario Rizzuto - Biochimica et biophysica acta (2009)
- S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. - Dong-Hyung Cho;Tomohiro Nakamura;Jianguo Fang;Piotr Cieplak;Adam Godzik;Zezong Gu;Stuart A Lipton - Science (New York, N.Y.) (2009)
- The Alzheimer's disease mitochondrial cascade hypothesis: an update. - Russell H Swerdlow;Shaharyar M Khan - Experimental neurology (2009)
- Protective effects of compound FLZ, a novel synthetic analogue of squamosamide, on beta-amyloid-induced rat brain mitochondrial dysfunction in vitro. - Fang Fang;Geng-tao Liu - Acta pharmacologica Sinica (2009)
- Amyloid precursor protein transgenic mouse models and Alzheimer's disease: understanding the paradigms, limitations, and contributions. - Tyler A Kokjohn;Alex E Roher - Alzheimer's & dementia : the journal of the Alzheimer's Association (2009)
... (138 更多 篇文献)
© 2025 MaltSci 麦伴科研 - 我们用人工智能技术重塑科研