High amyloid levels turn brain cells into saboteurs causing brain injuryRSS Feed
Specialised brain cells called astrocytes react to excess levels of leaked amyloid protein in the brain by changing their function from tissue nourishers to tissue assassins, a new study reported in the science new source ScienceDaily.com suggests.
High levels of amyloid are known to be associated with cumulative death of neurons in the brain, ultimately resulting in the progressive brain injury and brain shrinkage characteristic of Alzheimer’s disease. All neurons excrete the protein, especially with increasing age. However, amyloid excretion rises dramatically in Alzheimer’s.
The new research found that astrocytes, which normally deliver nutrients to brain cells and remove waste products, become inflamed and alter their activity when amyloid levels exceed a certain threshold. In particular, they bundle a lipid known as ceramide with a protein called PAR-4 into toxic vesicles called “apoxosomes” that kill both the astrocytes and surrounding brain cells.
Lead author Dr Erhard Bieberich, a biochemist at the Georgia Health Sciences University Medical College, explained that earlier studies pose something of a mystery: raised amyloid levels alone do not kill brain cells and cause brain injury, so another, secondary process must take place to make the protein toxic. If this did not occur, the cells would not produce the amyloid plaques characteristic of Alzheimer’s – they would die before being able to make them.
The mechanism Dr Bieberich and his colleagues have uncovered appears to be that secondary process. In an animal model, the team found that antibodies to PAR-4 and ceramide prevented the death of astrocytes when amyloid levels were excessive, a discovery that may lead to a new Alzheimer’s treatment in the future.
The study appears in the Journal of Biological Chemistry.
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