Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling.
Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling.
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DOI：
10.3389/fphar.2014.00120
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发表时间：
2014
影响因子：
5.6
通讯作者：
Calabrese V
中科院分区：
文献类型：
--
作者：
Cornelius C;Koverech G;Crupi R;Di Paola R;Koverech A;Lodato F;Scuto M;Salinaro AT;Cuzzocrea S;Calabrese EJ;Calabrese V
阿尔茨海默病（AD）和骨质疏松症是多因素的进行性退行性疾病。越来越多的证据表明，骨质疏松症和髋部骨折是AD患者常见的并发症，尽管这种关联的机制仍然知之甚少。活性氧（ROS）作为细胞内氧化还原信号分子参与骨代谢的调节，包括核因子-κB配体依赖性破骨细胞分化的受体激活剂，但它们也具有细胞毒性作用，包括脂质过氧化和对蛋白质和DNA的氧化损伤。ROS的产生涉及细胞应激反应机制的调节，是在编码氧化还原蛋白（称为维生素）的氧化还原敏感基因的控制下的整合的、高度调节的过程。维生素，编码蛋白质，如热休克蛋白（Hsps）Hsp 32，Hsp 70，硫氧还蛋白，和sirtuin蛋白，代表了一个系统，控制一个复杂的网络细胞内信号转导途径相关的寿命和参与保存细胞内稳态在应激条件下。同样，营养性抗氧化剂已通过维生素的激素依赖性激活证明其神经保护潜力。剂量-反应的生物学相关性影响了那些在治疗许多疾病中指向患者最佳剂量的策略。因此，热休克反应已成为一个重要的激素靶点的新的细胞保护策略，重点是能够调节应激反应机制的化合物的药理学发展。在这里，我们讨论了可能的信号转导机制参与激活的维生素，相关的骨重建和通过增强细胞的抗应激能力提供了一个合理的限制相关的有害后果的稳态破坏随之而来的影响老化过程。
Alzheimer’s disease (AD) and osteoporosis are multifactorial progressive degenerative disorders. Increasing evidence shows that osteoporosis and hip fracture are common complication observed in AD patients, although the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS) are emerging as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-κB ligand-dependent osteoclast differentiation, but they also have cytotoxic effects that include lipoperoxidation and oxidative damage to proteins and DNA. ROS generation, which is implicated in the regulation of cellular stress response mechanisms, is an integrated, highly regulated, process under control of redox sensitive genes coding for redox proteins called vitagenes. Vitagenes, encoding for proteins such as heat shock proteins (Hsps) Hsp32, Hsp70, the thioredoxin, and the sirtuin protein, represent a systems controlling a complex network of intracellular signaling pathways relevant to life span and involved in the preservation of cellular homeostasis under stress conditions. Consistently, nutritional anti-oxidants have demonstrated their neuroprotective potential through a hormetic-dependent activation of vitagenes. The biological relevance of dose–response affects those strategies pointing to the optimal dosing to patients in the treatment of numerous diseases. Thus, the heat shock response has become an important hormetic target for novel cytoprotective strategies focusing on the pharmacological development of compounds capable of modulating stress response mechanisms. Here we discuss possible signaling mechanisms involved in the activation of vitagenes which, relevant to bone remodeling and through enhancement of cellular stress resistance provide a rationale to limit the deleterious consequences associated to homeostasis disruption with consequent impact on the aging process.
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DOI：
10.1074/jbc.m110.157552
发表时间：
2010-11-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
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通讯作者：
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DOI：
10.1165/rcmb.2006-0340tr
发表时间：
2007-02-01
影响因子：
6.4
作者：
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通讯作者：
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影响因子：
2.8
作者：
Calabrese, Edward J.;Hoffmann, George R.;Nascarella, Marc A.
通讯作者：
Nascarella, Marc A.
影响因子：
2.8
作者：
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DOI：
10.1124/jpet.108.137455
发表时间：
2008-07-01
影响因子：
3.5
作者：
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