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Breakthrough reveals first ever complete structure of a nuclear hormone receptor on human DNA

For decades, scientists have been studying nuclear hormone receptors to gain a better understanding of how they turn genes on and off throughout the body and how they function as key drug targets for a number of diseases, such as diabetes, breast cancer, osteoporosis and high cholesterol. A new UVA Health System study, led by Fraydoon Rastinejad, Ph.D., professor of pharmacology and director of the UVA Center for Molecular Design and published in the October 29 issue of Nature, reveals the first ever complete structure of a nuclear hormone receptor on human DNA – a discovery that now clears a new path for scientists to design more effective drugs with fewer associated health risks. “Dr. Rastinejad’s findings fundamentally change the way people all over the world will study how nuclear hormone receptors work and introduces a new platform for designing better drugs,” says Jim Garrison, Ph.D., professor of pharmacology at UVA Health System. Nuclear hormone receptors, including the peroxisome proliferator-activated receptors (PPARs), are proteins that sit on the surface of cells and bind to specific hormones such as estrogen, progesterone and thyroid hormone. Once the receptor binds to its hormone and its DNA regulatory element, it can cause a number of alterations in the cell, switching genes on and off. These switches control the continual regulation of the metabolic system and reproductive tissues, as well as the development and differentiation of skin, bone and behavioral centers in the brain. “PPARs are widely studied because they regulate the genes that produce fat cells, glucose, insulin, lipids and metabolism,” says Dr. Rastinejad. “That’s what makes them such good drug targets for diseases like diabetes. We can design drugs more rationally to bind to the PPAR nuclear receptor complex to help regulate these functions in the body.” A number of diabetes drugs, called insulin sensitizers, have been developed based on that knowledge, but now that scientists have a clear view into how these receptors bind and what shape they take the door is wide open for the development of better drugs. "After 40 years of nuclear receptor research, we finally can view the first full and complete structure of a nuclear receptor, thanks to Dr. Rastinejad’s break-though achievement,” says Bert W. O’Malley, Ph.D., professor and chairman, Department of Molecular and Cellular Biology at Baylor College of Medicine who is widely considered a top expert in the field.

17 Nov 2008

10 symptoms that should never be ignored

Not every ache and pain merits a quick trip to the doctor -- but some do.

6 Nov 2008

Lithium carbonate to be tested for motor neurone disease

Victims of motor neurone disease (MND) will find hope from British research which has found that lithium carbonate, a cheap off-patent drug, may offer a treatment for the disease.

3 Nov 2008

Leukaemia drug may reverse multiple sclerosis brain damage

Scientists in Britain say a drug which was developed to treat leukaemia may also be a powerful new weapon against multiple sclerosis (MS).

23 Oct 2008

High salt levels in food banished by seaweed

High salt levels in processed food could be a thing of the past, thanks to new research which has found that a certain type of seaweed can be used as a natural, health boosting alternative that doesn't affect the taste or adversely affect the shelf life of the food.

From Sheffield Hallam University 21 Sep 2008

Atomic bomb's effect results in adult-onset thyroid cancer

Radiation from the atomic bomb blasts in Hiroshima and Nagasaki, Japan, in 1945, likely rearranged chromosomes in some survivors who later developed papillary thyroid cancer as adults, according to Japanese researchers.

1 Sep 2008

Epilepsy drug gabapentin may reduce insomnia in recovering alcoholics

It's a Catch-22 of the highest order. People with alcohol problems often use alcohol to get to sleep -- but it actually keeps them from getting good-quality sleep all night long.

4 Aug 2008

Amyloid plaques seen with conventional MRI in animal model for first time

For the first time, scientists have captured images of brain lesions similar to those found in Alzheimer's disease using clinical-grade MRI in an animal model of the disease, according to research reported at the Alzheimer's Association's 2008 International Conference on Alzheimer's Disease (ICAD 2008), in Chicago.

27 Jul 2008

New research shows that adrenal nodules not being adequately evaluated

A new study published in Endocrine Practice found that a substantial percentage of patients with nodules, or growths, in their adrenal glands were not being properly evaluated by physicians.

2 Jul 2008

Subclinical hypothyroidism common in chronic kidney disease

Many patients with chronic kidney disease (CKD) have mild reductions in thyroid function, or subclinical hypothyroidism-a condition that becomes more common as kidney function declines, according to a study in the September 2008 issue of Clinical Journal of the American Society of Nephrology (CJASN).

11 Jun 2008

New clinical research and imaging centre for Bristol

The University and United Bristol Healthcare Trust (UBHT) are joining forces to establish a new state-of-the-art Clinical Research and Imaging Centre (CRIC) at St Michael's Hospital on St Michael's Hill

21 May 2008

Forty-one percent of registered nurses find generics are less effective than name brand drugs say American Society of Registered Nurses

In a national online survey conducted by the American Society of Registered Nurses, 41% of the 781 Registered Nurses surveyed on April 28 reported that generic drugs are less effective than their equivalent brand-name counterparts.

5 May 2008

Low blood levels of vitamin D may be associated with depression in seniors

Older adults with low blood levels of vitamin D and high blood levels of a hormone secreted by the parathyroid glands may have a higher risk of depression, according to a report in the May issue of Archives of General Psychiatry.

5 May 2008

Thyrotropin levels may be associated with coronary heart disease mortality in women

Women with increasing levels of thyrotropin within the normal range appear to have a higher risk of fatal coronary heart disease, according to a report in the April 28 issue of Archives of Internal Medicine.

28 Apr 2008

New hope for blood disorder anaemia

A new understanding of how red blood cell production is controlled could lead to improvements in the treatment of the blood disorder anaemia, according to West Australian medical researchers.

13 Apr 2008

Discovery of new genetic links to psoriasis

In the first comprehensive study of the genetic basis of psoriasis, researchers at Washington University School of Medicine in St. Louis have discovered seven new sites of common DNA variation that increase the risk of the troublesome skin condition.

4 Apr 2008

Cardiovascular and metabolic issues in patients with thyroid dysfunction

Thyroid experts will present the latest information on cardiovascular and metabolic issues in patients with thyroid disorders, including those who have an underactive thyroid (hypothyroidism) or an overactive thyroid (hyperthyroidism), at a day-long scientific meeting on Friday, March 28, 2008 at the Marriott Metro Center in Washington, DC.

26 Mar 2008

Scans spot hidden tumors in Li-Fraumeni syndrome

Researchers at Dana-Farber Cancer Institute report that full-body PET/CT scanning detected unsuspected, treatable tumors in 3 of 15 patients with Li-Fraumeni syndrome (LFS), a rare genetic cancer syndrome for which no screening tests have been recommended.

19 Mar 2008

Inbred Romanian community provides insight into genetic factors associated with vitiligo

An isolated, inbred Romanian community has a higher than average frequency of the skin disease vitiligo and other autoimmune diseases, suggesting a genetic variation that may indicate susceptibility to the condition in a broader population, according to a report in the March issue of Archives of Dermatology, one of the JAMA/Archives journals.

18 Mar 2008

AstraZeneca completes enrollment in phase III studies of cancer drug vandetanib

AstraZeneca has announced that it has completed patient enrollment in two pivotal Phase III studies for vandetanib, the company's investigational, once-daily oral anti-cancer drug, for the second-line treatment of non-small cell lung cancer (NSCLC).

13 Mar 2008