HIV attack on brain cells points to new dementia treatments
17 Feb 2017
Scientists have discovered that a protein closely involved in AIDS-related dementia could provide clues for treating other forms of dementia.
A team of MRC-funded scientists from Cardiff University and researchers from University of California (UCLA) carried out a random screen of mice with different genetic mutations, which showed that some mice had better memory than others. Further tests revealed that the mice with better memory lacked a type of protein called the C-C chemokine receptor 5 (CCR5). Conversely, animals with too much CCR5 were slower to learn, revealing the impact of CCR5 on brain cells and their ability to code memories.
The team already knew that HIV uses the CCR5 protein to infect immune cells and that around 30 per cent of HIV-positive adults and 50 per cent of HIV-positive infants suffered from cognitive deficits.
AIDS-related dementia was previously thought to be caused by the effects of HIV on immune cells, creating inflammation and affecting the brain indirectly.
Having now witnessed the link between CCR5 and learning in mice, the team introduced to the brains of healthy mice i.e. those with normal levels of CCR5, the part of HIV that attaches to CCR5 (known as ‘V3’), and found that learning and memory decreased.
When the team introduced V3 to the brains of mice with reduced CCR5 levels, however, they identified no detrimental effects on learning and memory. This implies that HIV produces AIDS-related dementia directly by activating CCR5 thereby restraining brain cells from their usual ability to switch function (known as plasticity), which results in a failure to code memories properly.
The team therefore discovered that reducing CCR5 levels gave protection from AIDS-related dementia and that furthermore CCR5 only needed to be reduced in the neurones in order to confer protection.
Cardiff University’s Professor Kevin Fox, a senior author on the paper, explained: “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.”
Lead author on the paper Professor Alcino Silva of the David Geffen School of Medicine and Semel Institute for Neuroscience and Human Behaviour, said: "It is really exciting that drugs that inhibit CCR5, already on the market, could potentially be used to treat all sorts of memory deficits.”
Stuart Greenhill, Honorary Research Fellow at Cardiff University, added: “With the available CCR5 drugs on the market this work could have broad and immediate applicability across a range of neurological diseases.”
The original research paper, ‘CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory’ was published in eLife on 20 December 2016.
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