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Neurodegenerative Disorders: Problem in Waste Removal increases the Risk

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By Indrani Bhattacharyya | July 4, 2014 1:47 PM EST

The occurrence of dementia is on constant rise and for the health care sector, this trait is considered to be one of the toughest challenges to deal with.

Through a striking finding, an international team of scientists led by Professor Christian Haass and Gernot Kleinberger at the LMU's Adolf-Butenandt-Institute and the German Center for Neurodegenerative Diseases (DZNE) has now elucidated the mode of action of a genetic defect that contributes to the development of several different dementia syndromes.

Reuters
Neurodegenerative Disorders: Problem in Waste Removal increases the Risk

Alzheimer's and Parkinson's diseases display a number of common features. They are all characterised by the appearance in the brains of affected patients of abnormally high levels of insoluble protein deposits that are associated with massive loss of nerve cells. In order to minimise further damage to nerve cells in the vicinity of such deposits, dead cells and the proteinaceous aggregates released from them must be efficiently degraded and disposed of. This task is performed by specialised phagocytic cell or microglia that acts as "sanitary inspectors" in the brain to ensure prompt removal of debris.

The study, published in the journal Science Translational Medicine, talks about “specific mutations in the gene for a protein called TREM2, which regulates the uptake of waste products by microglia, lead to its absence from the cell surface. TREM2 is normally inserted into the plasma membrane of microglial cells such that part of it extends through the membrane as an extracellular domain. This exposed portion of TREM2 is responsible for the recognition of waste products left behind by dead cells. We believe that the genetic defect disrupts the folding of the protein chain soon during its synthesis in the cell so that it is degraded before it can reach the surface of the microglia.”

 “As a result, the amount of debris that the microglia can cope with is significantly reduced. Consequently, the toxic protein deposits, as well as whole dead cells, cannot be efficiently removed and continue to accumulate in the brain. This is expected to trigger inflammatory reactions that may promote further nerve-cell loss,, Kleinberger explained later.

"In addition, our findings may perhaps point to ways of slowing the rate of progression of these illnesses even after the manifestation of overt signs of dementia, which has not been possible so far," Haass was quoted saying.

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(Photo: Reuters / Juan Medina)
Neurodegenerative Disorders: Problem in Waste Removal increases the Risk
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