HIV Tat protein causing brain damage
Jul 12, 2009
"The dendrites begin to look like a patch of severely damaged trees after a bad ice storm." (EEEK!!) I thought it was my imagination that I was "losing it" mentally lately but once I read the articles on: "Researchers Identify Toehold For HIV's Assault On Brain".
I was not surprised-and it told me to really watch "how I was thinking". Memory dropouts and slow processing power are my key complaints. Age 53/Diag 1999 at 750,000 copies with 300 CD4/On Sutiva, Viread and Ziagen with Doxycline. Now 1,150 CD4 and UD. No OI's are majors. Question? Does Sustiva go thru the blood brain barrier and actually take out some of the HIV lurking in the brain? This is major news with as much as 50% or more of HIV'ers affected. I noticed it in older patients and it now looks as I am becoming one.
Ref: http://www.sciencedaily.com (use search or google) (please print full content of this question as it alerted me to something that hasn't been talked about very much and may help others.) Scientists have known that Tat, which helps HIV operate, replicate, and infect cells, is at the forefront of HIV's attack on the brain, bringing about severe inflammation. Immune cells within the brain go into overdrive, churning out substances that attract more immune cells, and white blood cells from the body flood in and join the fray, all clumping together to form destructive entities known as multinucleated giant cells.
"Suddenly the brain environment turns from nurturing to toxic, and the brain has to work much harder to send messages. Cells are on overdrive, spending a lot more energy to do the same things they used to do easily," said Gelbard, who is director of the Center for Neural Development and Disease at Rochester.
Other changes occur throughout the brain as well. Neurons that normally reach throughout the brain by forming networks of far-reaching, delicate extensions crucial for cell communication become damaged. Instead of sprouting healthy dendrites projections that resemble tiny trees neurons in the brain of an HIV patient have had parts of their dendrites abruptly torn off, in a process known as "synaptic pruning." The dendrites begin to look like a patch of severely damaged trees after a bad ice storm.
Such damage occurs in parts of the brain crucial for thinking, decision-making, and movement and memory. That accounts for symptoms like difficulties concentrating, forgetfulness, poor coordination, confusion, and gait disturbances. In later stages, neuroAIDS can cause outright dementia.
Gelbard's team discovered that Tat works through the ryanodine receptor to sicken neurons in two ways. Scientists have known that Tat makes vulnerable the mitochondria, organelles within neurons and other cells that are commonly considered the "power packs" or energy sources for cells. The team discovered that Tat destroys the ability of mitochondria to protect themselves from changes in levels of calcium.
The scientists discovered another effect of Tat as well. Tat has a dramatic effect on an organelle known as the endoplasmic reticulum, where proteins are actually assembled and folded. Gelbard's team discovered that it's Tat's effects on the ryanodine receptor that cause an "unfolded protein response" seen in the brains of HIV patients. Shape is everything for proteins, and they're nearly always useless or harmful when they are unfolded or misfolded. The problem in HIV patients is exacerbated because protein folding requires a great deal of energy energy that cells whose mitochondria are petering out aren't likely to have."--
Whew! Thanks for the sustiva question on the blood brain barrier. Mike
Response from Dr. Henry
Thanks for posting that. KH
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