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101.
Taylor DM Maxwell MM Luthi-Carter R Kazantsev AG 《Cellular and molecular life sciences : CMLS》2008,65(24):4000-4018
Sirtuins comprise a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that target multiple protein substrates to execute diverse biological functions. These enzymes are
key regulators of clinically important cellular and organismal processes, including metabolism, cell division and aging. The
desire to understand the important determinants of human health and lifespan has resulted in a firestorm of work on the seven
mammalian sirtuins in less than a decade. The implication of sirtuins in medically important areas such as diabetes, cancer,
cardiovascular dysfunction and neurodegenerative disease has further catapulted them to a prominent status as potential targets
for nutritional and therapeutic development. Here, we present a review of published results on sirtuin biology and its relevance
to human disease.
Received 25 June 2008; received after revision 20 August 2008; accepted 29 August 2008 相似文献
102.
Muñoz U Bartolomé F Esteras N Bermejo-Pareja F Martín-Requero A 《Cellular and molecular life sciences : CMLS》2008,65(21):3507-3519
It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading
to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer’s disease (AD) patients.
We previously reported that the anti-inflammatory 15- deoxy-Δ12,14-prostaglandin J
2 (15d-PGJ
2) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work
aimed at elucidating the mechanisms of 15d-PGJ
2-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2
by mechanisms dependent on PI3K/Akt activity. 15d-PGJ
2 prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory
subunit of PI3K. These effects of 15d-PGJ
2 were not mimicked by 9,10-dihydro-15-deoxy-Δ12,14- prostaglandin J
2, suggesting that 15d-PGJ
2 acts independently of peroxisome proliferator-activated receptor γ activation and that the α,β-unsaturated carbonyl group
in the cyclopentenone ring of 15d-PGJ
2 is a requisite for the observed effects.
Received 14 July 2008; received after revision 2 September 2008; accepted 12 September 2008 相似文献
103.
Liver X receptors in cardiovascular and metabolic disease 总被引:5,自引:0,他引:5
Liver X receptors (LXRs) α and β are nuclear oxysterol receptors and metabolic sensors initially found to regulate cholesterol
metabolism and lipid biosynthesis. Recent studies have elucidated the importance of LXR in the development of cardiovascular
diseases and metabolic disorders. LXR agonists prevent development of atherosclerosis by modulation of metabolic as well as
inflammatory gene expression in rodent models. Moreover, LXR activation inhibits hepatic gluconeogenesis and lowers serum
glucose levels, indicating possible application of LXR activation in the treatment of diabetes mellitus. However, first-generation
LXR agonists elevate hepatic and serum trigylceride levels, making subtype-specific agonists and selective LXR modulators
rather than unselective LXR agonists a potential pharmacological strategy. This review summarizes the multiple physiological
and pathophysiological implications of LXRs and observations that identify LXRs as potential targets for therapeutic interventions
in human cardiovascular and metabolic disease.
Received 30 August 2005; received after revision 10 October 2005; accepted 4 November 2005 相似文献
104.
Phytanic acid is a branched-chain fatty acid that accumulates in a variety of metabolic disorders. High levels of phytanic
acid found in patients can exceed the millimolar range and lead to severe symptoms. Degradation of phytanic acid takes place
by α-oxidation inside the peroxisome. A deficiency of its breakdown, leading to elevated levels, can result from either a
general peroxisomal dysfunction or from a defect in one of the enzymes involved in α-oxidation. Research on Refsum disease,
belonging to the latter group of disorders and characterized by a deficiency of the first enzyme of α-oxidation, has extended
our knowledge of phytanic acid metabolism and pathology of the disease greatly over the past few decades. This review will
centre on this research on phytanic acid: its origin, the mechanism by which its α-oxidation takes place, its role in human
disease and the way it is produced from phytol.
Received 4 October 2005; received after revision 24 February 2006; accepted 26 April 2006 相似文献
105.
Anti-amyloidogenic therapies: strategies for prevention and treatment of Alzheimer’s disease 总被引:1,自引:1,他引:0
Deposition of amyloid β-protein (Aβ) in the brain is an early and invariant neuropathological feature of Alzheimer’s disease
(AD). The current search for anti-AD drugs is mainly focused on modification of the process of accumulation of Aβ in the brain.
Here, we review four anti-amyloidogenic strategies: (i) reduction of Aβ production, which has mainly been approached with
secretase inhibition, (ii) promotion of the Aβ degrading catabolic pathway, including an Aβ degrading enzyme, neprilysin,
(iii) immunotherapy for Aβ and (iv) inhibition of Aβ aggregation. We have reported that AD patients have a favorable molecular
environment for Aβ aggregation and that various compounds, such as polyphenols, interfere with Aβ aggregation and destabilize
preformed Aβ fibrils.
Received 21 December 2005; received after revision 14 February 2006; accepted 29 March 2006 相似文献
106.
Lehmann F Tiralongo E Tiralongo J 《Cellular and molecular life sciences : CMLS》2006,63(12):1331-1354
Sialic acids consist of a family of acidic ninecarbon sugars that are typically located at the terminal positions of a variety
of glycoconjugates. Naturally occurring sialic acids show an immense diversity of structure, and this reflects their involvement
in a variety of biologically important processes. One such process involves the direct participation of sialic acids in recognition
events through specific interactions with lectins, a family of proteins that recognise and bind sugars. This review will present
a detailed overview of our current knowledge regarding the occurrence, specificity and function of sialic acid-specific lectins,
particularly those that occur in viruses, bacteria and non-vertebrate eukaryotes.
Received 13 December 2005; received after revision 9 February 2006; accepted 15 February 2006 相似文献
107.
Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance 总被引:3,自引:0,他引:3
Balaraman Y Limaye AR Levey AI Srinivasan S 《Cellular and molecular life sciences : CMLS》2006,63(11):1226-1235
Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading
cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the
serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in
the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review,
we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor
protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt,
Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.
Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006 相似文献
108.
目的探讨快速老化小鼠SAM-P/8的同向旋转现象与帕金森病动物模型的相关性。方法取发作旋转行为的7月龄雄性SAM-P/8和同源对照SAM-R/1小鼠各6只,分为旋转组和正常对照组两组,首先采用老化度评价标准对其老化度进行评定,其次根据帕金森病动物模型造模标准对其旋转行为进行评定。结果同月龄SAM-P/8的老化度高于SAM-R/1;SAM-P/8出现可重复的同向右侧旋转,频率为60 r/min,符合帕金森病动物模型造模成功的标准,SAM-R/1无旋转现象出现。结论初步认定SAM-P/8的同向旋转现象为类帕金森病现象,对帕金森病研究有重要意义。 相似文献
109.
目的观察恩替卡韦治疗失替偿期乙型肝炎肝硬化的疗效。方法对2006年3月至2007年6月18例来我院就诊乙型肝炎肝硬化失代偿期患者给予口服恩替卡韦治疗剂量0.5mg/次,1次/d,基本疗程1年。观察HBV-DNA定量,肝纤维化指标(HA、LN、POⅢ、Ⅳ—C),肝功能指标(ALT、AST、TBIL)变化情况。结果所有患者临床症状明显改善,肝功能指标、HBV—DNA定量、肝纤四项指标改善有非常显著差异(P〈0.01)。结论恩替卡韦治疗乙型肝炎失代偿期肝硬化可有效抑制病毒复制,改善肝功能,阻止肝纤维化进展,防止病情恶化。 相似文献
110.