NEUROBIOLOGY
Cellular metabolism linked to anxiety disorders
Anxiety disorders, ranging from social phobia to post-traumatic stress disorder, are the most common psychiatric diseases in the United States. Research in mice suggests a link between the gene that encodes Glyoxylase 1 (GLO1) and increased anxiety; however, the mechanism underlying this association has remained unclear. The normal role of GLO1 is to degrade cytotoxic byproducts of glycolysis, a function which has no obvious connection to anxiety. Margaret Distler and colleagues at the University of Chicago asked whether the primary substrate of GLO1, methylglyoxal, might have undocumented neurological effects. Using a mouse model, they demonstrated that methylglyoxal stimulates robust activity from GABAA receptors, which are neuron receptors that respond to neurotransmitters. As pharmaceuticals targeting GABAA receptors are mainstays of anxiety treatment, this study provides a definitive functional link between GLO1 activity and anxiety. The team also showed that the inhibition of GLO1 in mice reduced anxious behavior, suggesting GLO1 as a potential novel therapeutic target in humans. These findings have important clinical implications not only for anxiety disorders, but also for other central nervous system diseases having proposed associations with the gene encoding GLO1, including autism, affective disorders, and schizophrenia.
TITLE:
Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal
AUTHOR CONTACT:
Abraham Palmer
University of Chicago, Chicago, IL, USA
Phone: (773) 834-2897; E-mail: aap@uchicago.edu
View this article at: http://www.jci.org/articles/view/61319?key=e2db0ff64964217265c6
DEVELOPMENT
Hope for new treatment options for the rare disease Beare-Stevenson syndrome
p38 Inhibition ameliorates skin and skull abnormalities in Fgfr2 Beare-Stevenson mice
Ethylin Wang Jabs
Mount Sinai School of Medicine, New York, NY, USA
Phone: 212-241-3504; E-mail: Ethylin.Jabs@mssm.edu
View this article at: http://www.jci.org/articles/view/62644?key=0be3e3be09d197cc8279
VASCULAR BIOLOGY
To grow or not grow: how does Angiopoietin-2 differentially regulate?
Several studies have demonstrated that ANG-2 inhibits angiogenesis through down-regulation of tyrosine kinase 2 (TIE2). However, new research on tumor cells shows that ANG-2 promotes angiogenesis. These findings led Dr. Moritz Felcht and his colleagues from Heidelberg University in Germany to investigate the role of ANG-2 on angiogenesis in the absence of TIE2. Results from endothelial cell binding and adhesion assays show that ANG-2 binds to integrin receptors when TIE2 expression is low, resulting in increased cell migration and angiogenesis. Their study concluded that ANG2 inhibits and promotes angiogenesis by binding to TIE2 and integrin receptors, respectively. Their groundbreaking work provides insight on how ANG-2 differentially regulates angiogenesis, which has important implications for angiogenesis therapeutics involving ANG-2.
Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling
Hellmut Augustin
German Cancer Research Center (DKFZ-ZMBH Alliance) and Heidelberg Universit, Heidelberg, UNK, DEU
Phone: +49-(0)6221-42-1500; E-mail: augustin@angiogenese.de
View this article at: http://www.jci.org/articles/view/58832?key=c7cc0899a244305f6199
ONCOLOGY
Breast cancer stem cell revealed
Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis
Michael Andreeff
The Univ of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Phone: 713-792-7260; Fax: 713-794-1903; E-mail: mandreef@mdanderson.org
View this article at: http://www.jci.org/articles/view/59735?key=a4dcacf86339b739c2ee
IMMUNOLOGY
Too much of a good thing is bad: hormones protect from toxic inflammation
Glucocorticoid receptor dimerization induces MKP1 to protect against TNF-induced inflammation
Lien Dejager
VIB/DMBR, Ghent, , BEL
Phone: 093313705; E-mail: lien.dejager@dmbr.vib-ugent.be
View this article at: http://www.jci.org/articles/view/60006?key=5e53349c42253f156423
IMMUNOLOGY
Stop the attack: new treatment options for graft versus host disease
Antigen presenting cell-derived complement modulates murine graft versus host disease
Peter S. Heeger
Phone: 212.241.6500 (general number); Fax: ; E-mail: peter.heeger@mssm.edu
View this article at: http://www.jci.org/articles/view/61019?key=b796836c1a0d2ceed170
ONCOLOGY
Keeping liver cancer in check: a new therapeutic target for hepatocellular carcinoma
CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma
Tiebang Kang
Sun Yat-sen University Cancer Center, Guangzhou, , CHN
Phone: +86 2087343183; E-mail: kangtb@mail.sysu.edu.cn
View this article at: http://www.jci.org/articles/view/61380?key=bc88ef0895636e0346c8
Journal of Clinical Investigation