Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.
Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.
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DOI：
10.3390/biomedicines11082275
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发表时间：
2023-08-16
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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脑源性神经营养因子（BDNF）是一种主要的神经营养因子，其缺失或中断与进行性神经疾病的发病机制有许多交叉。亨廷顿舞蹈病（HD）是一种遗传性神经退行性疾病，以运动、精神和认知障碍为特征，与基底神经节功能障碍和纹状体投射神经元的最终死亡有关。对HD中导致BDNF丧失的机制的收集调查强调了这种神经营养因子对神经元活力的重要性，并呼吁关注治疗干预的机会。利用现有和即将开展的研究的电子数据库搜索，我们构建了一篇文献综述，其总体目标是探索HD中触发BDNF失调的各种分子事件。我们重点介绍了在HD临床前模型中研究这些主要机制的研究，并将这些研究与人类HD受试者中评估类似终点的研究联系起来。我们还特别关注了越来越多的文献，详细介绍了影响HD患者BDNF丰度的关键转录组学和表观遗传改变。最后，我们对拟议的神经营养因子导向疗法进行了批判性评估，并评估了寻求纠正HD患者BDNF表达的临床试验。
Brain-derived neurotrophic factor (BDNF) is a major neurotrophin whose loss or interruption is well established to have numerous intersections with the pathogenesis of progressive neurological disorders. There is perhaps no greater example of disease pathogenesis resulting from the dysregulation of BDNF signaling than Huntington’s disease (HD)—an inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive impairments associated with basal ganglia dysfunction and the ultimate death of striatal projection neurons. Investigation of the collection of mechanisms leading to BDNF loss in HD highlights this neurotrophin’s importance to neuronal viability and calls attention to opportunities for therapeutic interventions. Using electronic database searches of existing and forthcoming research, we constructed a literature review with the overarching goal of exploring the diverse set of molecular events that trigger BDNF dysregulation within HD. We highlighted research that investigated these major mechanisms in preclinical models of HD and connected these studies to those evaluating similar endpoints in human HD subjects. We also included a special focus on the growing body of literature detailing key transcriptomic and epigenetic alterations that affect BDNF abundance in HD. Finally, we offer critical evaluation of proposed neurotrophin-directed therapies and assessed clinical trials seeking to correct BDNF expression in HD individuals.
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影响因子：
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作者：
Mai M;Akkad AD;Wieczorek S;Saft C;Andrich J;Kraus PH;Epplen JT;Arning L
通讯作者：
Arning L
影响因子：
4.4
作者：
Agrawal, Sonal;Fox, Jonathan H.
通讯作者：
Fox, Jonathan H.
影响因子：
4.2
作者：
Ahveninena, Lotta M.;Stouta, Julie C.;Glikmann-Johnston, Yifat
通讯作者：
Glikmann-Johnston, Yifat
影响因子：
4.2
作者：
Maloney, Michael T.;Wang, Wei;Bhowmick, Sumana;Millan, Ivan;Kapur, Mridu;Herrera, Nicolas;Frost, Everett;Zhang, Elena Y.;Song, Scott;Wang, Melissa;Park, Amelia Bora;Yao, Annabelle Y.;Yang, Yanmin
通讯作者：
Yang, Yanmin
DOI：
10.1523/jneurosci.0865-12.2012
发表时间：
2012-07-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
Bachis A;Avdoshina V;Zecca L;Parsadanian M;Mocchetti I
通讯作者：
Mocchetti I