ApoD at a concentration of 10 mu g/ml partially prevented loss of MAP2 immunostaining and LDH release from injured hippocampal neurons after kainate injury. ApoD also attenuated the increase in oxidative products of arachidonic acid and cholesterol, GSK1904529A F-2-isoprostanes and 7-ketocholesterol, respectively, after kainate treatment. In view of the molecular structure of apoD which consists of an eight stranded beta barrel that forms a binding pocket for a number of small hydrophobic molecules, we propose that apoD promotes its neuroprotective effects by binding to arachidonic acid and cholesterol thus preventing their oxidation to neurotoxic products such as 4-hydroxynonenal

(4-HNE) and 7-ketocholesterol. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Oxidative stress and amyloid-P are considered major etiological and pathological factors in the initiation and promotion of neurodegeneration in Alzheimer disease (AD). Insomuch as causes of such oxidative stress, transition metals, such as iron and copper,

which are found in high concentrations see more in the brains of AD patients and accumulate specifically in the pathological lesions, are viewed as key contributors to the altered redox state. Likewise, the aggregation and toxicity of amyloid-P is dependent upon transition metals. As such, chelating agents that selectively bind to and remove and/or “”redox silence”" transition metals have long been considered as attractive therapies for AD. However, the blood-brain barrier and neurotoxicity of many traditional metal chelators has

limited their utility in AD or other neurodegenerative disorders. To circumvent this, we previously suggested that nanoparticles conjugated to iron chelators may have the potential to deliver chelators into the www.selleck.cn/products/pci-34051.html brain and overcome such issues as chelator bioavailability and toxic side-effects. in this study, we synthesized a prototype nanoparticle-chelator conjugate (Nano-N2PY) and demonstrated its ability to protect human cortical neurons from amyloid-p-associated oxidative toxicity. Furthermore, Nano-N2PY nanoparticle-chelator conjugates effectively inhibited amyloid-P aggregate formation. Overall, this study indicates that Nano-N2PY, or other nanoparticles conjugated to metal chelators, may provide a novel therapeutic strategy for AD and other neurodegenerative diseases associated with excess transition metals. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Proteinuria, inflammation, chronic hypoxia, and rarefaction of peritubular capillaries contribute to the progression of renal disease by affecting proximal tubular epithelial cells (PTECs). To study the transcriptional response that separates patients with a stable course from those with a progressive course of disease, we isolated PTECs by laser capture microdissection from cryocut tissue sections of patients with proteinuric glomerulopathies (stable n = 20, progressive n = 11) with a median clinical follow-up of 26 months.