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An aggresome is a proteinaceous inclusion body that forms when cellular degradation machinery is impaired or overwhelmed, leading to an accumulation of protein for disposal. The aggresomal response is believed to be a generalised-protective 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. This process involves the retrograde microtubule-based motor protein, dynein. Various proteins, such as the histone deacetylase 6 (HDAC6), are thought to act as adaptor protein between the dynein motor protein and accumulating polyubiquitinated substrate proteins. 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 formation of the aggresome is largely believed to be a protective response, sequestering potentially cytotoxic aggregates and also acting as a staging center for eventual autophagic clearance from the cell.
Human Disease
Certain cellular inclusions seen in human disease are thought to represent an aggresomal response, such as 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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