Deleterious Alteration of Glia in the Brain of Alzheimer's Disease.
Deleterious Alteration of Glia in the Brain of Alzheimer's Disease.
复制标题
DOI：
10.3390/ijms21186676
复制
发表时间：
2020-09-12
影响因子：
5.6
通讯作者：
Kim SS
中科院分区：
文献类型：
--
作者：
Kim E;Otgontenger U;Jamsranjav A;Kim SS
阿尔茨海默病（AD）中神经元的退化由皮质内的遗传、免疫和细胞因素引起。淀粉样蛋白β（Aβ）作为AD单一病因的传统共识随着爆炸性神经生物学证据的积累而不断修正。在AD的多方面损伤中，胶质细胞的参与因其对神经元的动态贡献而具有重要意义，无论是以神经保护还是神经毒性的方式。基本上，小胶质细胞和星形胶质细胞通过释放神经保护性细胞因子、在突触中维持足够量的谷氨酸和修剪过多的突触末端来促进神经元的可持续性。这种有益的作用转移到慢性神经炎症条件下的其他有害级联反应。在这种变化中，有新发现的特异性细胞因子、microRNA和互补因子。以前未知的离子通道，如Kv1.3，Kir2.1和HCN的机制也阐明了小胶质细胞的激活。胶质细胞的激活通过膜上表达的mGluRs使谷氨酸递质溢出而产生兴奋性毒性，从而导致突触功能障碍和吞噬。小胶质细胞和星形胶质细胞之间的通信是通过外泌体以及细胞因子介导的，其中许多遗传信息以microRNA的形式转移。新的发现告诉我们，AD条件下的神经元环境是一个更加复杂和动态相互作用的空间。识别环境和细胞通讯中的每个分子将有助于从神经生物学角度更好地理解AD，从而提出可能的治疗线索。
The deterioration of neurons in Alzheimer’s disease (AD) arises from genetic, immunologic, and cellular factors inside the cortex. The traditional consensus of the amyloid-beta (Aβ) paradigm as a singular cause of AD has been under revision, with the accumulation of exploding neurobiological evidence. Among the multifaceted casualties of AD, the involvement of glia gains significance for its dynamic contribution to neurons, either in a neuroprotective or neurotoxic fashion. Basically, microglia and astrocytes contribute to neuronal sustainability by releasing neuroprotective cytokines, maintaining an adequate amount of glutamate in the synapse, and pruning excessive synaptic terminals. Such beneficial effects divert to the other detrimental cascade in chronic neuroinflammatory conditions. In this change, there are new discoveries of specific cytokines, microRNAs, and complementary factors. Previously unknown mechanisms of ion channels such as Kv1.3, Kir2.1, and HCN are also elucidated in the activation of microglia. The activation of glia is responsible for the excitotoxicity through the overflow of glutamate transmitter via mGluRs expressed on the membrane, which can lead to synaptic malfunction and engulfment. The communication between microglia and astrocytes is mediated through exosomes as well as cytokines, where numerous pieces of genetic information are transferred in the form of microRNAs. The new findings tell us that the neuronal environment in the AD condition is a far more complicated and dynamically interacting space. The identification of each molecule in the milieu and cellular communication would contribute to a better understanding of AD in the neurobiological perspective, consequently suggesting a possible therapeutic clue.
登录
查看更多内容
影响因子：
16.2
作者：
Bhaskar, Kiran;Konerth, Megan;Kokiko-Cochran, Olga N.;Cardona, Astrid;Ransohoff, Richard M.;Lamb, Bruce T.
通讯作者：
Lamb, Bruce T.
影响因子：
25
作者：
Asai H;Ikezu S;Tsunoda S;Medalla M;Luebke J;Haydar T;Wolozin B;Butovsky O;Kügler S;Ikezu T
通讯作者：
Ikezu T
影响因子：
25
作者：
Filosa, Jessica A.;Bonev, Adrian D.;Nelson, Mark T.
通讯作者：
Nelson, Mark T.
影响因子：
5.5
作者：
Edwards, Justin P.;Zhang, Xia;Mosser, David M.
通讯作者：
Mosser, David M.
小胶质细胞构成一个阻止斑块周围神经毒性原纤维Aβ42热点的障碍。
影响因子：
16.6
作者：
Condello, Carlo;Yuan, Peng;Schain, Aaron;Grutzendler, Jaime
通讯作者：
Grutzendler, Jaime