Glutathione and thioredoxin dependent systems in neurodegenerative disease: What can be learned from reverse genetics in mice

Oxidative stress is a major common hallmark of many neurodegenerative disease such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and stroke. Novel concepts in our understanding of oxidative stress indicate that a perturbed redox circuitry could be strongly linked with the onset of such diseases. In this respect, glutathione and thioredoxin dependent antioxidant enzymes play a central role as key regulators due to the fact that a slight dysfunction of any of these enzymes leads to sustained reactive oxygen species (ROS) production. Apart from their classical role as ROS scavengers, some of these enzymes are also able to control post-translational modifications. Therefore, efficient control of ROS production and reversibility of post-translational modifications are critical as improper control of such events may lead to the activation of pathological redox circuits that eventually culminate in neuronal cell death. To dissect the apparently opposing functions of ROS in cell physiology and pathophysiology, a proper working toolkit is mandatory. In vivo modeling is an absolute requirement due to the complexity of redox signaling systems that often contradict data obtained from in vitro approaches. Hence, inducible/conditional knockout mouse models for key redox enzymes are emerging as powerful tools to perturb redox circuitries in a temporal and spatial manner. In this review we address the basics of ROS generation, chemistry and detoxification as well as examples in where applications of mouse models of important enzymes have been successfully applied in the study of neurodegenerative processes. We also highlight the importance of new models to overcome present technical limitations in order to advance in the study of redox processes in the role of neurodegeneration.     

Additions to knowledge of the Yellow-throated Glossy Cuckoo,Chrysococcyx flavigularis

Summary A series of eight specimens of the yellow-throated glossy cuckoo,Chrysococcyx flavigularis, recently collected in Bwamba Forest, western Uganda, and the field observations accompanying them give our first information on the courtship habits, call notes, and feeding range of the species, and extend our knowledge of its breeding season. It is now possible to demonstrate extensive sympatry withC. klaas, and also to present further details of its plumages.Zusammenfassung Eine unter Leitung vonR. Glen undA. Williams stehende Expedition zur Erforschung der isolierten Waldgebiete West-Ugandas konnte für das Los Angeles County Museum of Natural History im Bwamba-Urwald 8 Exemplare des noch wenig bekannten Gelbkehlkuckucks,Chrysococcyx flavigularis (Shelley), sammeln.Überdies ergab die Beobachtung der lebenden Vögel erstmals Aufschluß über Balzverhalten, Stimme und Nahrung dieses Kuckucks. Der Gonadenzustand der gesammelten Vögel legt im Verein mit den Feststellungen anderer Autoren die Annahme nahe, daß sich die Fortpflanzungszeit dieser Art über einen großen Teil des Jahres erstreckt.Chrysococcyx flavigularis kommt in einem ausgedehnten Gebiet neben der anscheinend nächstverwandten Art,Ch. klaas, vor; auch im Bwamba-Urwald leben beide sympatrisch. Die Maße der gesammelten Vögel werden angegeben und Einzelheiten der Gefiederfärbung und -zeichnung beschrieben.