Aggresome

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An aggresome is a body of protein which can form inside a cell. Aggresomes form when a cell's proteasome machinery faces an unusually high load of protein awaiting degradation, leading to an accumulation of protein for disposal.

The aggresomal response is believed to be a generalised cell biological response to the presence of a high load of abnormal or damaged protein within the cytosol of a cell which fails to be eliminated by the usual ubiquitin proteasome system for protein degradation..

An aggresome forms around the microtubule organizing center in eukaryotic cells, adjacent to or enveloping the cell's centrosomes. The protein in an aggresome is held in a cage made largely of intermediate filaments, for example the structural protein vimentin in many cells.

Typically, an aggresome forms in response to a cellular stress which generates a large amount of misfolded or partially denatured protein: hyperthermia, overexpression of an insoluble or mutant protein, etc. The aggresome may disappear – through proteasomal, lysosomal or autophagic degradation of the accumulated protein – if the load of defective proteins is reduced.

Human Disease

Certain cellular inclusions seen in human disease are thought to represent an aggresomal response for example the Lewy body seen in neurons in the brain in Parkinson's disease and Mallory's Hyaline seen in liver cells in conditions such as alcoholic liver disease.

References

Johnston, J.A., C.L. Ward, and R.R. Kopito. 1998. J. Cell Biol. 143:1883–1898;



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