Systemstudie Andere Entsorgungstechniken. Hauptband Abschlussbericht

SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Systemanalyse Mischkonzept. Abschlussbericht. Hauptband

Available from Kernforschungszentrum Karlsruhe G.m.b.H. (KfK) (DE). Projektgruppe Andere Entsorgungstechniken (PAE) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Systemanalyse Mischkonzept. Hauptband Abschlussbericht

TIB Hannover: FR 3495(Schl) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

PyrPeg, a Blood-Brain-Barrier-Penetrating Two-Photon Imaging Probe, Selectively Detects Neuritic Plaques, Not Tau Aggregates

© 2020 American Chemical Society. Amyloid-β (Aβ) tracers have made a significant contribution to the treatment of Alzheimer's disease (AD) by allowing a definitive diagnosis in living patients. Unfortunately, they also detect tau and other protein aggregates that compromise test accuracy. In AD research, there has been a growing need for in vivo Aβ imaging by two-photon microscopy, which enables deep-brain-fluorescence imaging. There is no suitable neuritic Aβ probe for two-photon microscopy. Here we report PyrPeg, a novel two-photon fluorescent probe that can selectively target insoluble Aβ rather than tau and α-synuclein aggregates in the AD model brain and postmortem brain. When injected intravenously, PyrPeg detects the neuritic plaques in the brain and olfactory bulb of the AD model. PyrPeg may serve as a useful blood-brain-barrier-penetrating diagnostic tool for optical and functional monitoring of insoluble forms of Aβ aggregates in the living AD brain11Nsci

Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer’s disease

Monoamine oxidase–B (MAO-B) has recently emerged as a potential therapeutic target for Alzheimer’s disease (AD) because of its association with aberrant -aminobutyric acid (GABA) production in reactive astrocytes. Although short-term treatment with irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. We show that prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). We have developed a potent, highly selective, and reversible MAO-B inhibitor, KDS2010 (IC 50 = 7.6 nM; 12,500-fold selectivity over MAO-A), which overcomes the disadvantages of the irreversible MAO-B inhibitor. Long-term treatment with KDS2010 does not induce compensatory mechanisms, thereby significantly attenuating increased astrocytic GABA levels and astrogliosis, enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice. Copyright © 2019 The Authors, some rights reserved11Nsci

Systemanalyse Mischkonzept. Thermische und thermomechanische Analysen des Endlager-Nahbereichs und Ermittlung des Flaechenbedarfs des Endlagers. Abschlussbericht. Technischer Anhang 5

Available from Kernforschungszentrum Karlsruhe G.m.b.H. (KfK) (DE) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman