Vexed mutations promote degeneration of dopaminergic neurons through excessive activation of the innate immune response.
Vexed mutations promote degeneration of dopaminergic neurons through excessive activation of the innate immune response.
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DOI：
10.1038/s41531-022-00417-5
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发表时间：
2022-11-02
影响因子：
8.7
通讯作者：
Babcock, Daniel T.
中科院分区：
文献类型：
--
作者：
Davis, Jacinta;Kolaski, Elizabeth;Babcock, Daniel T.
帕金森病（PD）的特征是大脑中多巴胺能（DA）神经元的缺失。然而，对于为什么DA神经元选择性地易受PD的影响，我们知之甚少。我们之前完成了一项筛选，确定了与DA神经元进行性变性相关的基因。在这里，我们描述了一个以前未被表征的基因CG42339在果蝇DA神经元丢失中的作用。CG42339突变体表现出DA神经元的进行性损失和运动功能障碍，以及大脑中晚期糖基化终产物（AGEs）的积累。基于这种表型，我们将CG42339称为vexed。我们证明，在皮层胶质细胞内，为了维持神经元的活力，特别需要vexed。烦恼功能的丧失导致大脑先天免疫反应的过度激活，导致DA神经元的丧失。我们发现先天免疫反应的激活导致一氧化氮信号的增加和AGEs的积累，最终导致神经退行性变。这些结果为免疫反应在中枢神经系统中的作用及其如何影响神经元活力之间的关系提供了进一步的见解。
The hallmark of Parkinson’s disease (PD) is the loss of dopaminergic (DA) neurons in the brain. However, little is known about why DA neurons are selectively vulnerable to PD. We previously completed a screen identifying genes associated with the progressive degeneration of DA neurons. Here we describe the role of a previously uncharacterized gene, CG42339, in the loss of DA neurons using Drosophila Melanogaster. CG42339 mutants display a progressive loss of DA neurons and locomotor dysfunction, along with an accumulation of advanced glycation end products (AGEs) in the brain. Based on this phenotype, we refer to CG42339 as vexed. We demonstrate that vexed is specifically required within cortex glia to maintain neuronal viability. Loss of vexed function results in excessive activation of the innate immune response in the brain, leading to loss of DA neurons. We show that activation of the innate immune response leads to increased nitric oxide signaling and accumulation of AGEs, which ultimately result in neurodegeneration. These results provide further insight into the relationship between the role of the immune response in the central nervous system and how this impacts neuronal viability.
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影响因子：
9.3
作者：
Giunta B;Fernandez F;Nikolic WV;Obregon D;Rrapo E;Town T;Tan J
通讯作者：
Tan J
影响因子：
3.3
作者：
Davis J;Da Silva Santos C;Zavala NC;Gans N;Patracuolla D;Fehrenbach M;Babcock DT
通讯作者：
Babcock DT
影响因子：
12.3
作者：
Cook RK;Christensen SJ;Deal JA;Coburn RA;Deal ME;Gresens JM;Kaufman TC;Cook KR
通讯作者：
Cook KR
DOI：
10.1097/01.jnen.0000179050.54522.5a
发表时间：
2005-09-01
影响因子：
3.2
作者：
Dalfó, E;Portero-Otín, M;Ferrer, I
通讯作者：
Ferrer, I
影响因子：
16
作者：
Hedengren, M;Åsling, B;Hultmark, D
通讯作者：
Hultmark, D