McNaught and colleagues reported recently that systemic administration of proteasome inhibitors PSI (Z-Ileu-Glu(OtBu)-Ala-Leu-CHO) or epoxomicin recapitulated many of the degenerative changes seen in Parkinson's disease including loss of striatal dopamine and cell loss in the substantia nigra, locus ceruleus, dorsal motor nucleus of the X cranial nerve, and nucleus basalis of Meynert. Intracytoplasmic inclusions resembling Lewy bodies were also described. All experiments administering PSI to rats using identical procedures and multiple attempts failed to induce any of the previously described changes. Furthermore, administration of PSI or epoxomicin to monkeys in an attempt to extend the model to a primate species failed. Currently, systemic proteasome inhibition is not a reliable model for Parkinson's disease.
Vascular endothelial growth factor (VEGF) is a potent peptide with well-documented pro-angiogenic effects. Recently, it has also become clear that exogenous administration of VEGF is neuroprotective in animal models of central nervous system diseases. In the present study, VEGF was incorporated into a sustained release hydrogel delivery system to examine its potential benefits in a rat model of Huntington's disease (HD). The VEGF-containing hydrogel was stereotaxically injected into the striatum of adult rats. Three days later, quinolinic acid (QA; 225 nmol) was injected into the ipsilateral striatum to produce neuronal loss and behavioral deficits that mimic those observed in HD. Two weeks after surgery, animals were tested for motor function using the placement and cylinder tests. Control animals received either QA alone or QA plus empty hydrogel implants. Behavioral testing confirmed that the QA lesion resulted in significant deficits in the ability of the control animals to use their contralateral forelimb. In contrast, the performance of those animals receiving VEGF was significantly improved relative to controls with only modest motor impairments observed. Stereological counts of NeuN-positive neurons throughout the striatum demonstrated that VEGF implants significantly protected against the loss of striatal neurons induced by QA. These data are the first to demonstrate that VEGF can be used to protect striatal neurons from excitotoxic damage in a rat model of HD.
Recently, the use of natural products for the synthesis of carbon dots (CDs) has received much attention. Herein, leftover kiwi (Actinidia Deliciosa) fruit peels were successfully turned into beneficial fluorescent carbon dots (KN-CDs) via the hydrothermal-carbonization route. KN-CDs 1 and KN-CDs 2 were prepared without and with ammonium hydroxide, respectively. KN-CDs 1 and KN-CDs 2 were systematically characterized by various analytical techniques. Synthesized KN-CDs showed spherical-shaped morphology with narrow size distribution and excellent optical properties with excitation-independent behaviors. The quantum yields of KN-CDs 1 and KN-CDs 2 were calculated as 14 and 19%, respectively. Additionally, the KN-CDs possess excellent prolonging and photostability. Because of the excellent optical properties of KN-CDs, they were utilized as fluorescent sensors. The strong fluorescence of the KN-CDs was selectively quenched by Fe3+ ion, and quenching behavior showed a linear correlation with the concentrations of Fe3+ ion. KN-CDs 1 and KN-CDs 2 showed the detection of Fe3+ ions within the concentration range of 5–25 µM with the detection limit of 0.95 and 0.85 µM, respectively. Based on the turn-off sensing by the detection of Fe3+ ions, KN-CDs would be a promising candidate as a selective and sensitive fluorescent sensor.
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