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微量元素与老年性痴呆 总被引:2,自引:1,他引:2
阐明了几种微量元素在人体内某些部位的含量变化及其对神经系统产生的影响 ,以及与阿尔茨海默病 (老年性痴呆病 ,AD)临床症状的关系。研究表明 ,一些AD发病机制诸如突触及神经元的丢失、细胞内神经原的缠结和细胞外的老年斑等 ,与病人体内某些微量元素含量的异常密切相关 ,而且影响机制复杂 ,途径多样。探明微量元素的作用机制 ,对AD病的防治和诊断意义重大 相似文献
2.
Paolo Zatta Tamas KissMario Suwalsky Guy Berthon 《Coordination chemistry reviews》2002,228(2):271-284
Aluminium has been known as a neurotoxic agent to experimental animals since the last century (Arch. Exp. Pharmacol. 40 (1897) 98). However, great interest arose in it bioinorganic chemistry as well biology when it was demonstrated to be the causative agent in pathologies related to the long-term dialysis treatment of uremic subjects with renal failure (Life Chem. 11 (1994) 197), and as a potential etiopathogenic cofactor for several neurodegenerative diseases. The inorganic biochemistry of aluminium is still largely to be discovered. In this review the pro-oxidative property of aluminium toward biological membrane will be presented and its implications in involvement in human pathology will be discussed in an interdisciplinary frame from the bioinorganic point of view. 相似文献
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Summary In the preceding paper we reported on a docking study with the SYSDOC program for predicting the binding sites of huperzine A in acetylcholinesterase (AChE) [Pang, Y.-P. and Kozikowski, A.P., J. Comput.-Aided Mol. Design, 8 (1994) 669]. Here we present a prediction of the binding sites of 1-benzyl-4-[(5,6-dimethoxy-1-indanon-2-yl)methyl]piperidine (E2020) in AChE by the same method. E2020 is one of the most potent and selective reversible inhibitors of AChE, and this molecule has puzzled researchers, partly due to its flexible structure, in understanding how it binds to AChE. Based on the results of docking 1320 different conformers of E2020 into 69 different conformers of AChE and on the pharmacological data reported for E2020 and its analogs, we predict that both the R- and the S-isomer of E2020 span the whole binding cavity of AChE, with the ammonium group interacting mainly with Trp84, Phe330 and Asp72, the phenyl group interacting mainly with Trp84 and Phe330, and the indanone moiety interacting mainly with Tyr70 and Trp279. The topography of the calculated E2020 binding sites provides insights into understanding the high potency of E2020 in the inhibition of AChE and provides hints as to possible structural modifications for identifying improved AChE inhibitors as potential therapeutics for the palliative treatment of Alzheimer's disease. 相似文献
4.
Rudin M Mueggler T Allegrini PR Baumann D Rausch M 《Analytical and bioanalytical chemistry》2003,377(6):973-981
Modern drug development requires technologies that allow rapid translation from the preclinical to the clinical stage. It is obvious that non-invasive imaging modalities such as magnetic resonance imaging (MRI) will play a central role in this regard. This article reviews the use of structural and functional MRI readouts for characterization of central nervous system (CNS) disorders and evaluation of the efficacy of potential CNS drugs. Examples comprise dementia of Alzheimer's type, cerebral ischemia, and neuroinflammation covering both clinical and preclinical aspects. In these examples MRI has been used to obtain relevant structural information on brain atrophy, on the location and extent of ischemic brain areas, and on the number and distribution of demyelinated plaques. These structural data are complemented by readouts assessing the functional consequences associated with the pathomorphological changes. In the last decade, MRI has evolved into a standard tool for the development of CNS drugs. With regard to target-specific/molecular imaging applications MRI is limited by its inherently low sensitivity; complementary imaging modalities utilizing optical and radionuclear reporter systems will thus be required. 相似文献
5.
阿尔茨海默病(AD)和轻度认知功能损伤(MCI)具有患者多、诊断难的特点,改进BP神经网络,提出自适应BP神经网络(ABP)进行100次AD和MCI诊断模拟,ABP神经网络的诊断正确率显著高于BP和RBF神经网络.采用留一法将101例正常人、200例MCI和90例AD患者的样本分为训练集和检测集,用ABP神经网络对其进行诊断模拟,总正确率达到73.91%. 相似文献
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应用分子动力学模拟方法研究了海藻糖抑制淀粉质多肽42(Aβ42)构象转变的分子机理.结果表明,海藻糖溶液浓度对Aβ42构象转变具有非常重要的影响.在水和低浓度海藻糖溶液(0.18mol·L-1)中,Aβ42可由初始的α-螺旋结构转变成β-折叠的二级结构;但海藻糖浓度为0.37mol·L-1时即可有效抑制Aβ42的构象转变.这是因为海藻糖利用其优先排阻作用使水分子在多肽周围0.2nm内富集,而其自身却在距离多肽0.4nm的位置附近团聚.另外,海藻糖还可通过降低多肽间的疏水相互作用,减少多肽分子内远距离的接触,有效抑制多肽的疏水塌缩和构象转变.上述分子模拟的结果对于进一步合理设计阿尔茨海默病的高效抑制剂具有非常重要的理论指导意义. 相似文献
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Jia-Kuo Liu Wei Gu Xiao-Rui Cheng Jun-Ping Cheng Wen-Xia Zhou Ai-Hua Nie 《中国化学快报》2015,26(10):1327-1330
Based on the lead compound 1 reported in literature, a series of novel BACE1 inhibitors were designed and synthesized, among which compound 11 exhibited a 14-fold improvement in potency over the lead compound 1. This represents a good lead for the discovery of more promising BACE1 inhibitors for the potential treatment of AD. 相似文献
9.
Design and synthesis of 5-cyclopropyl substituted cyclic acylguanidine compounds as BACE1 inhibitors
Jia-Kuo Liu Wei Gu Xiao-Rui Cheng Jun-Ping Cheng Ai-Hua Nie Wen-Xia Zhou 《中国化学快报》2016,27(10):1626-1629
By taking compound 1 as a lead, a series of 5-cyclopropyl substituted cyclic acylguanidine compounds were designed and synthesized as BACE1 inhibitors, compound 4d exhibited 84-fold improved inhibition efficiency than lead compound 1. The diphenyl fragment at the P3 position and the substituents at the second phenyl ring were essential for the compounds to achieve improved inhibition efficiency. This SAR studies provides new insights into the design and synthesis of more promising BACE1 inhibitors for the potential treatment of AD. 相似文献
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阿尔茨海默症药物的开发对该疾病的治疗非常重要。利用纳米金为探针研究了13种化合物抑制Cu~(2+)诱导的β-淀粉样蛋白聚集的能力,筛选出了10种有效的抑制剂,并获得了抑制剂抑制能力与其分子结构间的关系,利用筛选出的抑制剂实现了β淀粉样蛋白聚集过程的抑制和H_2O_2产生量的减少,对阿尔茨海默症的研究具有重要意义。 相似文献