Public Release: 

JCI table of contents, April 6, 2006

JCI Journals


Hunting down the causes of Huntington disease

Huntington disease (HD) is a degenerative brain disease in which brain cells called neurons die as a result of aggregations of the polyQ-huntingtin protein. Symptoms include involuntary movements, personality changes, and dementia, and unfortunately, there is no effective treatment to delay or prevent HD. In a study appearing April 6 in advance of print publication in the May issue of the Journal of Clinical Investigation, researcher Sandrine Humbert and colleagues at the Institut Curie in France, report that a promising candidate HD drug, cystamine, is able to reduce neuron death and HD symptoms in animals by increasing levels of a protective protein called HSJ1b. The authors found that brains from patients with HD have significantly lower levels of HSJ1b, and that overexpressing HSJ1b in neurons grown in a laboratory dish protects them from polyQ-huntingtin-induced death. Next the researchers created worms that had neuron dysfunction due to the presence of polyQ-huntingtin, and found that the dysfunction could be reduced by HSJ1b. To identify the mechanism by which cystamine and HSJ1b were protective, the researchers gave cystamine to mice and found that cystamine increased not only levels of HSJ1b, but also levels of BDNF, an important neuron survival factor. These results were confirmed when the authors gave a related, FDA-approved drug, cysteamine, to mice and monkeys with HD. Together these studies reveal that cystamine and cysteamine raise BDNF in an HSJ1b-dependent manner and may be useful as potential treatments for HD.

TITLE: Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase

Sandrine Humbert
Institut Curie, Orsay, France
Phone: 33-169-86-30-69; Fax: 33-169-07-45-25; E-mail:
View the PDF of this article at:


Tracking the cells involved in virally-induced Kaposi sarcoma

Human herpesvirus 8 (HH8), also called Kaposi sarcoma herpesvirus, can induce lesions (wounds) and tumors as a result of inflammation, and formation of new blood vessels (a process called angiogenesis) in Kaposi sarcoma (KS), the most common malignancy in patients with HIV/AIDS. Previous reports show that mice that are genetically engineered to express vGPCR, a viral protein expressed during HH8 infection, go on to develop a disease that resembles KS, but the cellular mechanisms are unclear. Now, in a study appearing April 6 in advance of print publication in the May issue of the Journal of Clinical Investigation, Sergio A. Lira and colleagues at Mount Sinai School of Medicine in New York, report that vGPCR targets endothelial cells (which line blood vessel walls), stimulating endothelial cell growth and tumor formation directly. The authors used a traceable form of vGPCR to determine that the cells that were vGPCR-positive also expressed endothelial cell markers and angiogenic factors, proving that they were endothelial cells. Next the authors transferred vGPCR-expressing cells from the ears of mice to the tails of immune-suppressed mice, resulting in the formation of tumors in the recipients, and observed the accumulation of vGPCR-expressing cells in lesions over time. This work suggests that vGPCR directly stimulates proliferation of endothelial cells and that it is centrally involved in the formation of blood vessels and tumors in KS.

TITLE: The human herpesvirus 8 chemokine receptor vGPCR triggers autonomous proliferation of endothelial cells

Sergio A. Lira
Mount Sinai School of Medicine, New York, New York, USA
Phone: (212) 659-9404; Fax: (212) 849-2525; E-mail:
View the PDF of this article at:


ACE-ing the test of diabetes

Although individuals with high blood pressure are often prescribed drugs known as angiotensin-converting enzyme (ACE) inhibitors, higher ACE levels are also correlated with increased risk of other diseases such as diabetic kidney damage, breast cancer, and Alzheimer's disease. Importantly, ACE inhibitors show beneficial effects in these disorders apart from any effects on blood pressure. One target of ACE is a protein called bradykinin, and it is hypothesized that kidney damage associated with high ACE levels may be due to bradykinin action. In a study appearing April 6 in advance of print publication in the May issue of the Journal of Clinical Investigation, Oliver Smithies and colleagues at the University of North Carolina at Chapel Hill, report that compared to mice with diabetes alone, diabetic mice that do not have the bradykinin receptor (so that cells are unable to respond to bradykinin) show accelerated cellular senescence, a type of cellular inactivity. The researchers detected dramatic hair loss, osteoporosis, thin skin, kyphosis (curvature of the spine), oxidative stress, and reduced sperm development in male mice with the dual genetic defect (diabetes plus loss of bradykinin receptor). When the researchers looked at the expression of genes involved in aging and cell death (processes associated with cellular senescence) they identified several key genes that were more highly expressed in the double mutants. The authors note that the symptoms of cell senescence detected in the double mutant animals are similar to complications that occur in patients with diabetes, suggesting that loss of bradykinin receptor signaling is involved in the metabolic defects associated with this disease, as well as during the aging process.

TITLE: Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors

Oliver Smithies
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Phone: (919) 966-6913; Fax: (919) 966-8800; E-mail:
View the PDF of this article at:


Forget me not: chronic infection triggers autoimmune disease

Early childhood infections are hypothesized to predispose susceptible individuals to autoimmune diseases such as multiple sclerosis and juvenile diabetes. Previous studies have shown that although adult mice infected with a virus called LCMV respond with a vigorous immune response in which "cytotoxic T lymphocyte cells" (CTLs) eliminate the virus and provide lifelong protective immune memory, exposure to the same virus in newborn mice stimulates the development of CTLs that "tolerate" the virus, allowing lifelong viral persistence. Now, in a study appearing April 6 in advance of print publication in the May issue of the Journal of Clinical Investigation, Daniel D. Pinschewer and colleagues at University Hospital of Zürich, report a new mechanism to explain the link between viral infection and autoimmune disease. The authors demonstrate that direct infection of the brains of newborn, but not adult mice, with a virus called rLCMV/INDG is associated with virus control in peripheral tissues by the immune system, viral persistence in the brain, with no overt clinical symptoms. However, this brain-restricted, persistent viral disease makes the mice susceptible to T cell-mediated pathology and clinical disease following a subsequent peripheral challenge with a related LCMV virus. The authors hypothesize that the organ-restricted infection results from either an infection during the newborn stage or from simultaneous exposure to a second virus (such as herpesvirus or measles), and that the virus that infects the newborn may establish an infection within the brain more readily due to the immaturity of the blood-brain barrier.

TITLE: "Viral déjà vu" elicits organ-specific immune disease independent of reactivity to self

Daniel D. Pinschewer
University Hospital of Zürich, Zürich, Switzerland
Phone: 41-1-2552989; Fax: 41-1-2554420; E-mail:
View the PDF of this article at:


Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.