Alleviation of Huntington pathology in mice by oral administration of food additive glyceryl tribenzoate.
Alleviation of Huntington pathology in mice by oral administration of food additive glyceryl tribenzoate.
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通过口服食品添加剂三苯甲酸甘油减轻小鼠亨廷顿舞蹈症的病理。
DOI：
10.1016/j.nbd.2021.105318
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发表时间：
2021-06
影响因子：
6.1
通讯作者：
Pahan K
中科院分区：
文献类型：
--
作者：
Dutta D;Majumder M;Paidi RK;Pahan K
亨廷顿氏病（HD）是一种神经退行性疾病，其特征是突变亨廷顿蛋白的积累和纹状体和皮层神经元的显著丧失。除了运动困难外，HD患者还表现出焦虑和认知丧失。不幸的是，临床批准的药物只提供症状缓解，并不是没有副作用。本研究强调了fda批准的食品调味成分甘油三酯（GTB）在缓解转基因N171-82Q小鼠HD病理中的重要性。口服GTB可显著降低纹状体、运动皮层和海马的突变亨廷顿蛋白水平，增加活神经元的完整性。此外，我们发现苯甲酸钠（NaB）的存在，这是一种fda批准的用于尿素循环障碍和甘氨酸脑病的药物，在gtb喂养的HD小鼠的大脑中。因此，NaB也能显著降低纹状体和皮层的亨廷顿蛋白水平。发现神经胶质细胞的激活与HD大脑受影响区域的神经元死亡是一致的。有趣的是，GTB和NaB治疗都抑制了大脑中神经胶质细胞的激活和炎症。最后，GTB和NaB的神经保护作用可改善HD小鼠的运动表现。总的来说，这些结果表明GTB和NaB可能被重新用于HD。
Huntington’s disease (HD) is a neurodegenerative disorder characterized by accumulation of mutant huntingtin protein and significant loss of neurons in striatum and cortex. Along with motor difficulties, the HD patients also manifest anxiety and loss of cognition. Unfortunately, the clinically approved drugs only offer symptomatic relief and are not free from side effects. This study underlines the importance of glyceryl tribenzoate (GTB), an FDA-approved food flavoring ingredient, in alleviating HD pathology in transgenic N171–82Q mouse model. Oral administration of GTB significantly reduced mutant huntingtin level in striatum, motor cortex as well as hippocampus and increased the integrity of viable neurons. Furthermore, we found the presence of sodium benzoate (NaB), a FDA-approved drug for urea cycle disorders and glycine encephalopathy, in the brain of GTB-fed HD mice. Accordingly, NaB administration also markedly decreased huntingtin level in striatum and cortex. Glial activation is found to coincide with neuronal death in affected regions of HD brains. Interestingly, both GTB and NaB treatment suppressed activation of glial cells and inflammation in the brain. Finally, neuroprotective effect of GTB and NaB resulted in improved motor performance of HD mice. Collectively, these results suggest that GTB and NaB may be repurposed for HD.
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影响因子：
6
作者：
Christian F;Smith EL;Carmody RJ
通讯作者：
Carmody RJ
影响因子：
6.2
作者：
Khasnavis, Saurabh;Pahan, Kalipada
通讯作者：
Pahan, Kalipada
影响因子：
16.8
作者：
Crotti A;Glass CK
通讯作者：
Glass CK
影响因子：
6.2
作者：
Jana, Arundhati;Modi, Khushbu K.;Roy, Avik;Anderson, John A.;van Breemen, Richard B.;Pahan, Kalipada
通讯作者：
Pahan, Kalipada
影响因子：
3
作者：
Kaushik, Deepak Kumar;Basu, Anirban
通讯作者：
Basu, Anirban