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Sep 28, 2007

Gene’s Role in Protein Aggregation in Dementia Discovered

  • Researchers at the Mayo Clinic in Jacksonville discovered how loss of a gene, progranulin, can lead to accumulation of toxic TDP-43 proteins in the brain, which results in frontal temporal dementia (FTD).

    Previous research indicated that a form of FTD not caused by tau accumulation in neurons was due to mutations in the progranulin gene. Another study showed that TDP-43, which in its normal state is believed to help genes produce proteins, clogs brains of patients with FTD and amyotrophic lateral sclerosis.

    In the current study, the Mayo scientists investigated whether progranulin is involved in TDP-43 processing. Suppressing progranulin expression in neurons led to errant splicing of TDP-43 by the caspase 3 enzyme. When cut, these TDP-43 fragments move into the body of the cell and begin to stick together and form a thicket that grows and eventually disrupts the normal functioning of the neuron, the Mayo team reports.

    The study appears in the September 26 issue of the Journal of Neuroscience.



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