There is life with HIV

HIV can cause cognitive impairment of the brain by "disturbing the order" and impairing disposal of "cellular waste".

Reizweiterleitung in den NervenzellenHIV'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

Eu costumo dizer que, "ao longo da vida, morri mil mortes". E, de fato, creio que já ultrapassei esta cifra e não consigo deslindar, em vaticínios, quantas mortes eu viverei (...) até que chegeu, por acréscimo de misericórdia, a morte do carro físico. O fato é que toda a vez que posto um texto que se refere aos danos que o HIV causa ao cérebro e à rede neural, eu milito em causa própria, posto que, desde o início, quando mminha infecção primária por HIv configurou-se numa meningite, ele, o vírus, tem atuado de forma paulatina e silenciosa no meu cérbro (eu vejo minha lucidez esvaindo-se a pouco e pouco) e na minha rede neural (...) e Deus sabe o nível de concentração que é necessário para que eu não cometa erros de digitação, para que eu não perca o fio da meada em meus raciocínios e o quanto eu sofro com s dores, físicas e morais, da Neuroparia Periférica quem me corroi o sistema nervoso. Entretanto, apesar dos pesares, e de ter morrido tantas vezes, eu gosto de pensar que a morte do carro físico venha como esa da ilustração, envidando esforços hercúleos para me alcançar, arrastando-se como uma lesma, travestida de caracol....
I usually say that, “throughout my life, I died a thousand deaths”. And, in fact, I believe that I have already surpassed this figure and I am not able to unravel, in predictions, how many deaths I will live (...) until the death of the physical car arrived, in addition to mercy. The fact is that every time I post a text that refers to the damage that HIV causes to the brain and the neural network, I fight for my own cause, since, from the beginning, when my primary HIV infection was configured in a meningitis, he, the virus, has been acting slowly and silently in my brain (I see my lucidity gradually disappearing) and in my neural network (…) and God knows the level of concentration that is necessary for I do not make typos, so that I do not lose the thread of my reasoning and how much I suffer from the pains, physical and moral, of Peripheral Neuropathy who corrode my nervous system. However, despite the regrets, and having died so many times, I like to think that the death of the physical car comes as this illustration, making Herculean efforts to reach me, crawling like a snail, dressed in snails….

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.

Imageeses Imagees Image morees more Image morees more Image morees use Image morees morees morees usees more more use Image moreeseses Imagees more Image more use

"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.

Anatomy of an animal cellThe 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

Reference

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.

Another source

B Ward, of the University of California San Diego. Image morees use Image more use Image Imagees Press release. FEBRUARY 3, 2015.

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