The Brighton and Hove Aids Memorial (Photo credit: Dominic Alves).
Science

Breakthrough in understanding of AIDS-related dementia

by Paul Hilleard

Researchers from Cardiff University and the University of California (UCLA) have made a breakthrough in the understanding of AIDS-related dementia, discovering the role of a neuron protein which was also found to affect learning abilities in healthy subjects.

Professor Kevin Fox who led the work at Cardiff University’s School of Biosciences said: “Our work represents a major change in the understanding of how AIDS-related dementia works…”

“Armed with the new knowledge that the CCR5 protein in neurons affects learning and plays a major role in AIDS-related dementia, we can now look at ways to suppress it for treatment of the disease and investigate whether its reduction can also benefit other forms of dementia and even aid recovery for stroke victims.” Kevin Fox, Professor.

The new research started out as a random behavioural screen of mice at UCLA, revealing some mutant mice had better memory than others. Further tests revealed the mice with better memory lacked CCR5 proteins in their neurons. Conversely, animals that over-expressed CCR5 protein were slower to learn, revealing the impact of CCR5 on neurons and their ability to code memories.

C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells is involved in the immune system as it acts as a receptor for chemokines. This is the process by which T cells are attracted to specific tissue and organ targets. Many forms of HIV, the virus that causes AIDS, initially use CCR5 to enter and infect host cells.

Having witnessed the link between CCR5 and learning in their behavioural screen of mice, the team reasoned that activation of the protein in neuron cells by HIV infection might decrease neuron function and learning. When they introduced to the brain the part of HIV that attaches to CCR5 they found that learning and memory was decreased in normal mice, implying that HIV is likely to produce AIDS-related dementia by increasing the natural levels of CCR5 activity and restraining the cells from their usual plasticity function, resulting in a failure to code memories properly.

Professor Alcino Silva, David Geffen School of Medicine and Semel Institute for Neuroscience and Human Behavior talked about how “amazed” he was by the new discovery, “It is really exciting that drugs that inhibit CCR5, already on the market, could potentially be used to treat all sorts of memory deficits!”

Approximately 30% of HIV-positive adults and 50% of HIV-positive infants suffer from cognitive deficits – a significant clinical problem associated with HIV infection. It was previously thought that AIDS-related dementia was caused by the effects of HIV on immune cells, affecting the brain indirectly by attacking the immune system and creating inflammation. However, in light of this new discovery, the many scientist and researchers involved have broadened our understanding of the way AIDS – related dementia and other cognitive deficiencies are entwined. Miou Zhou, a UCLA scientist, claimed “Our findings signal a major turnaround on how we imagine treating cognitive problems associated with AIDS.”

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