HIV's Tat protein interferes with autophagy, a process by which damaged or unnecessary cells are broken down and eliminated, according to research published in the 4 from fevebreiro by neuroscience officer. This interruption may lead to neuronal injury, but immunosuppressive drugs such as rapamycin were able to reverse this process in a mouse study.
Although severe AIDS dementia has become rare in the age of effective antiretroviral therapy, many people with HIV can still develop milder cognitive problems associated with HIV, a disorder that can interfere with everyday life.
Jerel Campos and Eliezer Masliah of the University of California San Diego and their colleagues sought to determine how HIV deregulates the "autophagy Tat"In the laboratory through animal studies. They found that Tat binds to proteins in neurons that play a key role in the series of chemical reactions that determine autophagy, allowing damaged proteins (cell junk) to accumulate. In addition, they demonstrated that rapamycin has reduced neurodegeneration in mice, which could help prevent cognitive impairment.
Below is the edition of an excerpt from a release Press Releases from the University of California San Diego Describing the research and its results in more detail.
The researchers identified the main underlying mechanisms associated with HIV / associated cognitive disorders
Although antiretroviral therapies have significantly improved and extended the lives of many HIV patients, they suffer from another insidious and little discussed threat in the "aging
HIV-related cognitive disorders (HAND). The disorders, which most often reach patients with HIV with more 50 years of age, and can result in cognitive impairment, from mild to severe, making daily tasks a remarkable challenge.
But the new findings, published today by researchers at the University of California, San Diego School of Medicine, open the door to the development of new therapies to block or decrease cognitive decline due to MAO, which is estimated to affect 10% to 50% % of HIV patients at some age.
The study was published in the February 4 edition of the Journal of Neuroscience. More morees more Image Image Image more more Image more Jerel Adão Campos, PhD, a postdoctoral fellow by researcher Masliah lab, is the first author.
"Most people know that HIV affects the immune system, the ability to fight disease, but they may not be aware that HIV penetrates the brain and can damage brain cells," said Masliah, a researcher on HIV neurological behavior. , from the Neurological Behavior Research Center at UC San Diego.
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"Most of the cases we see are mild to moderate," said Masliah.
However, even mild cognitive problems can interfere with individual daily functionality and reduce the quality of life for these people, he added, noting that patients may have difficulty with daily activities such as controlling a checkbook or driving errors.
Morees more! Use Image more more use more Image Image use more more They focused on the tat protein of HIV, which interferes in a critical process of discarding cellular waste in neurons, known as autophagy.
"Neurons produce a lot of proteins, as part of their normal functions, some of which are damaged and need to be removed," said Masliah.
"Autophagy acts like a garbage disposal by removing and destroying damaged proteins."
Masliah and colleagues found that the tat protein do HIV "Steals" the process of elimination by interfering with the main paths. “HIV's tat protein is secreted by infected cells in the brain, and then they enter neurons that bind to a protein that is important for various autophagy processes,” explained Campos. "This neuronal connection disrupts the autophagy process, resulting in the accumulation of damaged proteins and the consequent death of the neuron, which can lead to impaired cognitive abilities".
To counteract this disorder, Campos said the team conducted studies using the cancer drug, rapamycin, in mice, which has been reported to promote autophagy in other cell types. "With the acceleration of neuronal autophagy, we hoped to nullify the damaging effects of the HIV tat protein on the process," he said.
The experiments produced positive results. "We found that rapamycin reduced the incidence of neurodegeneration in mice and in cell models," said Campos. While the feasibility of using rapamycin as a neurological treatment in humans is currently inconclusive, Campos said the results are exciting because they prove, in principle, that tat-induced autophagy reinforcement reduces neurodegeneration.
"With an understanding of how the molecular bases of proteins and HIV kill nerve cells, we can design drugs that can block this process," said Masliah.
Posted on Thursday, 05 2015 February
Translated by Claudio Souza, Reviewed by Mara Macedo on the 12 July 2015 of the original in HIV May Cause Cognitive Impairment by Disrupting Brain's Garbage Disposal
[youtube = ”https://www.youtube.com/watch?v=r8D16C6-D5M”%5D
J Campos, W Dumaop, S Elueteri, et al. HIV-1 Tat alters Neuronal autophagy through Autophagosome Fusion modulation for lysosome: implications for neurocognitive disorders related to HIV, Journal of Neuroscience 35 (5): 1921-1938. February 4 2015.
B Ward, of the University of California San Diego. Image morees use Image more use Image Imagees Press release. FEBRUARY 3, 2015.