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Progranulin Deletion or Mutation Leads to Toxic Proteins Build-up in Neurons

Filed in archive Genomics, Proteomics and Bioinformatics by ruth on September 28, 2007

Progranulin Deletion or Mutation Leads to Toxic Proteins Build-up in Neurons

Researchers have discovered that a deletion of a gene for progranulin leads to the accumulation of toxic proteins in the brain which subsequently results to dementia.
In the Sept. 26 issue of the Journal of Neuroscience, the scientists demonstrate that absence of a gene known as progranulin leads to errant splicing of a protein that usually operates within the nucleus of a nerve cell (neuron). When cut these proteins move into the body of the cell, and begin to stick together and form a thicket that grows, eventually disrupting the normal functioning of the neuron, the researchers say.

Clumps of this protein, TDP-43, have been found in a number of older age dementias, including Alzheimer's Disease (AD), Frontal Temporal Dementia (FTD), and in Amyotrophic lateral sclerosislinks (ALS).

The scientists also found that mutation or suppression of progranulin expression leads to an increase in the activity of caspase, which cleave and lead to the accumulation f TDP-43. The speculate that "progranulin could be acting a protective chaperone where it binds to TDP-43, and may protect it from cleavage."

Source: Mayo Clinic


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Tags: neurology  AD  ALS  proteomics  genomics  biotech  toxic+proteins  build+neurons 

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