The ageing population and concurrent rise in neurodegenerative disorders is drawing attention to the way that lipids (fats) are metabolised in the brain and how certain proteins can accumulate, forming ‘biological garbage’ that increases the risk of developing Alzheimer’s disease (AD).
In 2007, a group of researchers led by dual National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) fellow, Professor Brett Garner, attracted worldwide attention by showing that a protein called ABCA1 (ATP-binding cassette transporter A1) played a role in controlling the production of a small protein or ‘peptide’ called amyloid-beta (Aβ), which is generated in the lipid membranes of cells and which can accumulate in the brain, causing neuron death.
The researchers went on to identify that a closely-related protein, ABCA7, which is highly expressed in human brain cells, could also slow down the production of the Aβ peptide in cultured cells.
Now they have discovered that ABCA7 may play a role in removing toxic substances from the brain. By deleting the gene in a mouse model of AD, they showed that the disease pathology significantly worsened, indicating that the gene is, indeed, involved in regulating Aβ homeostasis and plaque load.
“This is the first study to describe the impact that a loss of ABCA7 function has in the brain in the AD context and may help us to understand why mutations in human ABCA7 confer increased risk for AD,” Professor Garner said.
“This research opens up new avenues for us to study how Aβ is removed from the brain and what therapeutic approaches may be used to promote this in the AD context.”
The paper, entitled ‘Deletion of Abca7 increases cerebral amyloid-β accumulation in the J20 mouse model of Alzheimer’s disease’ has just been published in the high-impact Journal of Neuroscience (6 March, 2013).
“We will now focus on discovering compounds that may selectively increase the expression of ABCA7 in the brain and in particular in the brain’s ‘garbage collector’ cells called microglia,” Professor Garner said.
“While we can only speculate that these compounds will promote the removal of the harmful Aβ deposits, our data lends support to the general concept that any approach aimed at increasing microglial phagocytosis – the process by which microglia digest Aβ and other unwanted materials – could be helpful in the AD treatment context.”
The study was conducted at the Illawarra Health and Medical Research Institute on the University of Wollongong campus and represents part of a long-term collaboration between Professor Garner (Principal Investigator) and Dr Hongyun Li with Dr Tim Karl and Dr Woojin Kim from Neuroscience Research Australia.
Media enquiries: IHMRI Communications Coordinator, Robyn Gower. P: 02 4252 8228. E: firstname.lastname@example.org; Professor Garner: P. 02 4298 1576. E. email@example.com
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