Reactive oxygen species (ROS) is massively produced in the brain after cerebral ischemia and reperfusion. It reacts strongly with cellular components, which has detrimental effects and leads to neuronal cell death. DJ-1, which was found to be the causative gene of familial Parkinson's disease PARK7, is a multifunction protein, which plays a key role in transcriptional regulation, and a molecular chaperone. In this study, we investigated the neuroprotective effect of DJ-1 against neurodegeneration caused by ischemia/reperfusion injury. Cerebral ischemia was induced in rats by 120 mins of middle cerebral artery occlusion (MCAO) using an intraluminal introduction method. The intrastriatal injection of recombinant glutathione S-transferase-tagged human DJ-1 (GST-DJ-1) markedly reduced infarct size in 2,3,5-triphenyltetrazolium chloride staining at 3 days after MCAO. In addition, we performed a noninvasive evaluation of ischemic size using magnetic resonance imaging and found a significant reduction of infarct size with the administration of GST-DJ-1. In GST-DJ-1-treated rats, behavioral dysfunction and nitrotyrosine formation were significantly inhibited. Furthermore, GST-DJ-1 markedly inhibited H 2 O 2 -mediated ROS production in SH-SY5Y cells. These results indicate that GST-DJ-1 exerts a neuroprotective effect by reducing ROSmediated neuronal injury, suggesting that DJ-1 may be a useful therapeutic target for ischemic neurodegeneration.
Imparting multiple functions to nanoparticles through organic functionalization has been attracting significant interest, particularly in terms of biomedical applications. Among them, diamond nanoparticles;the so-called nanodiamond (ND);have been recognized as one of the best platforms, because of its nontoxic or low-toxicity properties, as well as its organic characteristics that enable covalent bonding with introduced functionalities. Here, we show multistep organic transformations on the ND surface that amass the requisite functions layer by layer through covalent bonds. The functionalities introduced onto the ND surface were well-characterized by solution-phase 1 H NMR and 13 C NMR spectroscopies, recently developed by us and other groups, as well as conventional infrared (IR), fluorescence microscopy and spectroscopy, and elemental analysis. As a result, hydrophilic and fluorescent characteristics were incorporated onto the ND surface by adding polyethylene glycol (PEG) and fluorescein segments, providing fluorescent ND stably dispersed under a physiological environment. ND has been confirmed to be viable for use as a cellular imaging agent by introducing them into HeLa cells.
Immunization with amyloid-b (Ab) peptides, a therapeutic approach in Alzheimer's disease (AD), reduces brain Ab, and microglial Ab phagocytosis has been proposed as an Ab-lowering mechanism. We transplanted rat microglia into the rat lateral ventricle just after intra-hippocampal Ab injection, and then investigated the contribution of exogenous microglia to Ab clearance. Migration of exogenous microglia from the lateral ventricle to Ab plaque was detected by magnetic resonance imaging and histochemical analysis, and the clearance of Ab was increased by transplantation. These results suggest the possible usefulness of exogenous microglia to the therapeutic approach in AD.
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