Elucidating the Interactive Roles of Glia in Alzheimer's Disease Using Established and Newly Developed Experimental Models.
Elucidating the Interactive Roles of Glia in Alzheimer's Disease Using Established and Newly Developed Experimental Models.
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DOI：
10.3389/fneur.2018.00797
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发表时间：
2018
影响因子：
3.4
通讯作者：
Cho H
中科院分区：
文献类型：
--
作者：
Chun H;Marriott I;Lee CJ;Cho H
阿尔茨海默病（AD）是一种不可逆的神经退行性疾病，其确切病因尚不清楚。其特点是长时间的临床前和前症期，病理特征包括淀粉样蛋白- β (a β)肽积聚到脑实质的细胞外a β斑块中，以及由于微管相关tau蛋白的异常磷酸化导致神经元内细胞内神经原纤维缠结（nft）的形成。此外，先天免疫细胞的显著激活也被观察到和/或随后出现明显的神经炎症。虽然这种神经炎症反应可能通过清除神经毒性因子以神经保护方式起作用，但它们也可能具有神经毒性，通过促炎介质和氧化应激水平升高以及神经递质水平改变导致神经退行性变，从而导致病理症状，包括突触和认知障碍、神经元死亡、记忆减退以及新皮层和海马功能障碍。胶质细胞，特别是活化的小胶质细胞和反应性星形胶质细胞，似乎在这种二元反应中起着关键的相互作用。越来越多的证据清楚地表明，它们在包括阿尔茨海默病在内的神经退行性疾病的预防、发生和进展中起着关键作用。在这里，我们回顾了最近关于星形胶质细胞-小胶质细胞相互作用在AD背景下神经退行性变中的作用的研究结果，并讨论了新开发的体外和体内实验模型，这些模型将能够更详细地分析胶质细胞相互作用。对神经胶质细胞作用的进一步了解和新的探索工具的发展可能对早期AD预防和治疗的新干预措施的发展至关重要。
Alzheimer's disease (AD) is an irreversible neurodegenerative illness and the exact etiology of the disease remains unknown. It is characterized by long preclinical and prodromal phases with pathological features including an accumulation of amyloid-beta (Aβ) peptides into extracellular Aβ plaques in the brain parenchyma and the formation of intracellular neurofibrillary tangles (NFTs) within neurons as a result of abnormal phosphorylation of microtubule-associated tau proteins. In addition, prominent activation of innate immune cells is also observed and/or followed by marked neuroinflammation. While such neuroinflammatory responses may function in a neuroprotective manner by clearing neurotoxic factors, they can also be neurotoxic by contributing to neurodegeneration via elevated levels of proinflammatory mediators and oxidative stress, and altered levels of neurotransmitters, that underlie pathological symptoms including synaptic and cognitive impairment, neuronal death, reduced memory, and neocortex and hippocampus malfunctions. Glial cells, particularly activated microglia and reactive astrocytes, appear to play critical and interactive roles in such dichotomous responses. Accumulating evidences clearly point to their critical involvement in the prevention, initiation, and progression, of neurodegenerative diseases, including AD. Here, we review recent findings on the roles of astrocyte-microglial interactions in neurodegeneration in the context of AD and discuss newly developed in vitro and in vivo experimental models that will enable more detailed analysis of glial interplay. An increased understanding of the roles of glia and the development of new exploratory tools are likely to be crucial for the development of new interventions for early stage AD prevention and cures.
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影响因子：
9.3
作者：
Cherry JD;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK
DOI：
10.1523/jneurosci.1064-09.2009
发表时间：
2009-10-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Abdul HM;Sama MA;Furman JL;Mathis DM;Beckett TL;Weidner AM;Patel ES;Baig I;Murphy MP;LeVine H 3rd;Kraner SD;Norris CM
通讯作者：
Norris CM
影响因子：
168.9
作者：
Cagnin, A;Brooks, DJ;Banati, RB
通讯作者：
Banati, RB
影响因子：
4.2
作者：
Benzing, WC;Wujek, JR;Brunden, KR
通讯作者：
Brunden, KR
影响因子：
9.3
作者：
Carter, Stephen F.;Scholl, Michael;Nordberg, Agneta
通讯作者：
Nordberg, Agneta