Recent advances in the treatment of neurodegenerative diseases based on GSH delivery systems.
Recent advances in the treatment of neurodegenerative diseases based on GSH delivery systems.
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DOI：
10.1155/2012/240146
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发表时间：
2012
影响因子：
--
通讯作者：
Pinnen F
中科院分区：
文献类型：
--
作者：
Cacciatore I;Baldassarre L;Fornasari E;Mollica A;Pinnen F
神经退行性疾病，例如帕金森病 (PD) 和阿尔茨海默病 (AD)，是一组以某些脑细胞群进行性和特异性丧失为特征的疾病。氧化应激、线粒体功能障碍和细胞凋亡在这些疾病中发挥着相互关联的作用。有充分证据表明，自由基氧化损伤，特别是对神经元脂质、蛋白质、DNA 和 RNA 的损伤，在 PD 和 AD 大脑中广泛存在。此外，大脑中谷胱甘肽（GSH）代谢的改变与氧化应激和神经退行性疾病有关。因此，在这些病理中观察到的 GSH 水平降低促使许多研究人员寻找维持或恢复 GSH 水平的新潜在方法。不幸的是，由于稳定性差和生物利用度低，谷胱甘肽向中枢神经系统（CNS）的输送受到限制。基于药物化学和技术的方法通常用于改善治疗剂的物理化学、生物制药和药物递送特性。本文将主要关注这些用于补充细胞内谷胱甘肽水平的方法，细胞内谷胱甘肽水平在神经退行性疾病中会降低。在这里，我们讨论这些方法的有益特性及其对神经退行性疾病（尤其是 PD 和 AD）患者未来治疗的潜在影响。
Neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease(AD), are a group of pathologies characterized by a progressive and specific loss of certain brain cell populations. Oxidative stress, mitochondrial dysfunction, and apoptosis play interrelated roles in these disorders. It is well documented that free radical oxidative damage, particularly on neuronal lipids, proteins, DNA, and RNA, is extensive in PD and AD brains. Moreover, alterations of glutathione (GSH) metabolism in brain have been implicated in oxidative stress and neurodegenerative diseases. As a consequence, the reduced GSH levels observed in these pathologies have stimulated a number of researchers to find new potential approaches for maintaining or restoring GSH levels. Unfortunately, GSH delivery to the central nervous system (CNS) is limited due to a poor stability and low bioavailability. Medicinal-chemistry- and technology-based approaches are commonly used to improve physicochemical, biopharmaceutical, and drug delivery properties of therapeutic agents. This paper will focus primarily on these approaches used in order to replenish intracellular GSH levels, which are reduced in neurodegenerative diseases. Here, we discuss the beneficial properties of these approaches and their potential implications for the future treatment of patients suffering from neurodegenerative diseases, and more specifically from PD and AD.
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影响因子：
5.8
作者：
Aumelas, A.;Serrero, A.;Leonard, M.
通讯作者：
Leonard, M.
DOI：
10.3390/molecules15031242
发表时间：
2010-03-03
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Cacciatore I;Cornacchia C;Pinnen F;Mollica A;Di Stefano A
通讯作者：
Di Stefano A
DOI：
10.1007/bf03159937
发表时间：
1991-06-01
期刊：
MOLECULAR AND CHEMICAL NEUROPATHOLOGY
影响因子：
--
作者：
ADAMS, JD;KLAIDMAN, LK;MILLER, CA
通讯作者：
MILLER, CA
DOI：
10.1016/s0014-827x(02)01232-6
发表时间：
2002-06-01
期刊：
FARMACO
影响因子：
--
作者：
Brunetti, L;Cacciatore, I;Spirito, A
通讯作者：
Spirito, A
DOI：
10.1016/s0014-827x(03)00135-6
发表时间：
2003-09-01
期刊：
Farmaco (Lausanne)
影响因子：
--
作者：
Cacciatore, I.;Caccuri, A. M.;Sozio, P.
通讯作者：
Sozio, P.