Signaling interactions among neurons impact cell fitness and death in Alzheimer's disease.
Signaling interactions among neurons impact cell fitness and death in Alzheimer's disease.
复制标题
DOI：
10.4103/1673-5374.354516
复制
发表时间：
2023-04
影响因子：
6.1
通讯作者：
Singh A
中科院分区：
文献类型：
--
作者：
Yeates C;Deshpande P;Kango-Singh M;Singh A
阿尔茨海默病的病理涉及一个漫长的临床前阶段，在此期间大脑变化的特征性临床症状无法被检测到。在临床前阶段，内稳态机制可能有助于防止广泛的细胞死亡。有证据表明，患病神经元的选择性细胞死亡可能具有保护作用。随着疾病的进展，调控细胞死亡的信号通路失调导致神经退行性变。在由β - 淀粉样蛋白42或tau介导的神经退行性变的阿尔茨海默病人类和动物模型中，已确定c - Jun N - 末端激酶通路的异常激活。在果蝇中对一部分神经元中的β - 淀粉样蛋白42进行的克隆嵌合研究表明，表达β - 淀粉样蛋白42的细胞和野生型细胞之间存在复杂的相互作用。这篇综述探讨了c - Jun N - 末端激酶信号在细胞竞争以及表达β - 淀粉样蛋白42的神经元和野生型神经元之间的短距离信号相互作用中的作用。细胞竞争是一种保守的现象，它通过评估细胞相对于其邻近细胞的适应性并消除次优细胞来调节组织完整性。与基因不同的神经元细胞群并列的β - 淀粉样蛋白42体细胞克隆为研究神经退行性变带来了希望。生成带有标记的表达β - 淀粉样蛋白42或tau的克隆以及野生型神经元的基因嵌合体，将使我们能够了解短距离信号改变如何触发神经元细胞死亡，从而促进阿尔茨海默病的进展。这些方法有可能发现用于早期检测阿尔茨海默病的生物标志物以及新的干预治疗靶点。
The pathology of Alzheimer’s disease involves a long preclinical period, where the characteristic clinical symptoms of the changes in the brain are undetectable. During the preclinical period, homeostatic mechanisms may help prevent widespread cell death. Evidence has pointed towards selective cell death of diseased neurons playing a potentially protective role. As the disease progresses, dysregulation of signaling pathways that govern cell death contributes to neurodegeneration. Aberrant activation of the c-Jun N-terminal kinase pathway has been established in human and animal models of Alzheimer’s disease caused by amyloid-beta 42- or tau-mediated neurodegeneration. Clonal mosaic studies in Drosophila that examine amyloid-beta 42 in a subset of neurons suggest complex interplay between amyloid-beta 42-expressing and wild-type cells. This review examines the role of c-Jun N-terminal kinase signaling in the context of cell competition and short-range signaling interactions between amyloid-beta 42-expressing and wild-type neurons. Cell competition is a conserved phenomenon regulating tissue integrity by assessing the fitness of cells relative to their neighbors and eliminating suboptimal cells. Somatic clones of amyloid-beta 42 that juxtapose genetically distinct neuronal cell populations show promise for studying neurodegeneration. Generating genetic mosaics with labeled clones of amyloid-beta 42- or tau-expressing and wild-type neurons will allow us to understand how short-range signaling alterations trigger cell death in neurons and thereby contribute to the progression of Alzheimer’s disease. These approaches have the potential to uncover biomarkers for early Alzheimer’s disease detection and new therapeutic targets for intervention.
登录
查看更多内容
DOI：
10.1038/s41576-020-0262-8
发表时间：
2020-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Baker NE
通讯作者：
Baker NE
DOI：
10.3233/jad-179941
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Cline EN;Bicca MA;Viola KL;Klein WL
通讯作者：
Klein WL
影响因子：
4.3
作者：
Costa-Rodrigues C;Couceiro J;Moreno E
通讯作者：
Moreno E
影响因子：
4.6
作者：
Blair, SS
通讯作者：
Blair, SS
影响因子：
8.8
作者：
Coelho, Dina S.;Schwartz, Silvia;Moreno, Eduardo
通讯作者：
Moreno, Eduardo