Toehold behind HIV's brain assault identified

Washington, November 15 : Scientists have uncovered a number of events that take place after brain cells are infected by HIV, a virus whose assault on the nervous system continues unabated despite antiviral medications.

Researchers from the University of Rochester Medical Center and other institutions say that they have been successful in reversing the effects of Tat, a protein that is central to HIV's attack on cells called neurons, in the laboratory.

The scientists attribute their success to the discovery of the receptor that Tat uses to attack neurons. They say that it was by blocking this receptor that they could reverse the effects of Tat.

Writing about their work in the journal PloS One, the team insist that their work opens up a new avenue for exploring ways to prevent or treat HIV's neurological effects, for which there is no currently approved treatment.

Funded by the National Institute of Mental Health, the latest research project aims at finding out the first treatment for the neurological effects of HIV, known collectively as neuroAIDS or HIV dementia.

Dr. Harris Gelbard, a neurologist at the University of Rochester Medical Center, has revealed that Tat works through the ryanodine receptor to sicken neurons in two ways: by destroying the ability of mitochondria to protect themselves from changes in levels of calcium, and by affecting an organelle known as the endoplasmic reticulum, where proteins are actually assembled and folded.

The researcher says that it is Tat's effects on the ryanodine receptor that cause an "unfolded protein response" seen in the brains of HIV patients.

Gelbard says that the new findings are in line with past studies that showed that the central problem in HIV dementia is not that brain cells simply die, but rather they become sick and lose their ability to communicate with each other.

Since the cells are still alive, according to Gelbard, there is hope that the condition could be stopped or even reversed with proper treatment.

The researcher has revealed that the team were able to stop the harmful effects of Tat in neurons from mice by using the drug dantrolene, which blocks the ryanodine receptor.

Gelbard, however, cautions that dantrolene has side effects and thus may not be appropriate for use in people.

"A lot of people are under the impression that HIV has been 'solved,' that somehow, it's no longer a problem. But the disease never went away, and it's a huge problem," said Gelbard, who is professor of Neurology, Pediatrics, and Microbiology and Immunology.

"There are a fair number of similarities between this brain disease and other diseases, such as Parkinson's or Alzheimer's. We hope that what we are learning can be applied to other diseases as well," the researcher added.

ANI