EDITOR’S PICK: Antioxidants decrease disease in a Drosophila model of Alzheimer’s disease
Alzheimer’s disease (AD) is one of a number of neurodegenerative disorders in which brain cells damaged by naturally occurring chemicals known as reactive oxygen species (ROS) have been observed. However, whether this oxidative damage causes neurodegeneration or is a consequence of it has not been previously determined. A study appearing online on December 14, in advance of publication in the January print issue of the Journal of Clinical Investigation, indicates that oxidative damage is a factor contributing to neurodegeneration in a Drosophila model of neurodegenerative disorders such as AD.
Mel Feany and colleagues from Brigham and Women’s Hospital and Harvard Medical School assessed neuron cell death in Drosophila expressing a neurodegenerative disease–associated form of the human protein tau. The number of dying neurons was increased if these insects were also genetically modified to have high levels of ROS. By contrast, if the insects were treated with the antioxidant vitamin E they had decreased numbers of dying neurons. This demonstration that oxidative stress contributes to neurodegeneration in this model of AD suggests that targeting antioxidant pathways might provide a new approach for treating individuals with AD and other related neurodegenerative disorders.
TITLE: Oxidative stress mediates tau-induced neurodegeneration in Drosophila.
AUTHOR CONTACT:
Mel B. Feany
Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Phone: (617) 525-4405; Fax: (617) 525-4422; E-mail: mel_feany@hms.harvard.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=28769
BONE BIOLOGY: IFN-gamma tips towards bone destruction
The soluble factor IFN-gamma has been shown to both promote and inhibit bone destruction, but the mechanisms by which it mediates these opposing effects and which effect predominates in vivo have not been clearly established. Using mice, researchers from Emory University have shown that in vitro, IFN-gamma directly inhibits the differentiation of cells that destroy bone (osteoclasts) and indirectly promotes their differentiation. In this study, which appears online on December 14 in advance of publication in the January print issue of the Journal of Clinical Investigation, Roberto Pacifici and colleagues further demonstrated that the in vitro indirect effects of IFN-gamma were a result of this soluble factor increasing the activity of APCs, thereby increasing T cell activation and production of the pro-osteoclastogenic factors RANKL and TNF-alpha. Importantly, the bone destroying effects of IFN-gamma were found to predominate in vivo in 3 distinct models of bone loss (osteoporosis). It is therefore possible that targeting IFN-gamma might provide a new approach to prevent bone loss in individuals with osteoporosis.
TITLE: IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation
AUTHOR CONTACT:
Roberto Pacifici
Emory University, Atlanta, Georgia, USA.
Phone: (404) 712-8420; Fax: (404) 727-1300; E-mail: roberto.pacifici@emory.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=30074
ONCOLOGY: A new way to stop FoxM1 promoting tumor growth
The initiation of tumors in the liver of mice using a combination of toxic chemicals has previously been shown to require a protein known as FoxM1. In a study using the same mouse model of liver cancer, which appears online on December 14 in advance of publication in the January print issue of the Journal of Clinical Investigation, researchers from the University of Illinois at Chicago show that FoxM1 is also required for tumor cell growth, making it a potential therapeutic target for the treatment of liver cancer.
Galina Gusarova and colleagues showed that deletion of the mouse gene encoding FoxM1 after tumors had formed but while tumors were still growing, caused a substantial decrease in the number of tumors in the liver. A similar decrease was observed when mice with pre-existing tumors were treated with a cell-penetrating peptide inhibitor of FoxM1, ARF26–44. Further analysis showed that ARF26–44 treatment increased tumor cell death by a process known as apoptosis and decreased tumor cell proliferation. Importantly, ARF26–44 treatment affected only the tumor cells, and not the normal liver tissue, leading the authors to conclude that ARF26–44 is an effective therapeutic approach to limit the progression of liver cancer in mice. Further studies will be required to determine whether this approach is viable for the treatment of human liver cancer.
TITLE: A cell-penetrating ARF peptide inhibitor of FoxM1 in mouse hepatocellular carcinoma treatment
AUTHOR CONTACT:
Galina A. Gusarova
University of Illinois at Chicago, Chicago, Illinois, USA.
Phone: (312) 996-6994; Fax: (312) 355-4010; E-mail: gusarova@uic.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=27527
Journal
Journal of Clinical Investigation