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.

Bio-genesis

Typically, an aggresome forms in response to a cellular stress which generates a large amount of misfolded or partially denatured protein: hyperthermia

Hyperthermia

Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...

, 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.
Aggromsome formation is believed to

An aggresome forms around the microtubule organizing center

Microtubule organizing center

The microtubule-organizing center is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spindle apparatus, which separate the chromosomes during cell...

 in eukaryotic

Eukaryote

A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 cells, adjacent to or enveloping the cell's centrosome

Centrosome

In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center of the animal cell as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden in 1883...

s. Lysine linked (63) polyubitiuntation tags the protein for retrograde transport via HDAC6 binding and microtubule-based motor protein, dynein. The protein aggregate is transported through the microtubule and unloaded via p97 forming the aggresome. Mediators such as p62 are believed to be involved in aggrosome formation in sequestering omega-somes, which bind and increase the size of the aggreseome. The aggreseome is eventually targeted for autophagic clearance for the cell. Some pathological proteins, such as a-synuclein, cannot be degraded and cause the aggresomes to form inclusion body's, or in parkinsons Lewy bodys, which contribute to neuronal dysfunction and death.

Human Disease

Certain cellular inclusions seen in human disease are thought to represent an aggresomal response, such as the Lewy body

Lewy body

Lewy bodies are abnormal aggregates of protein that develop inside nerve cells in Parkinson's disease , Lewy Body Dementia and some other disorders. They are identified under the microscope when histology is performed on the brain....

 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

Alcoholic liver disease

Alcoholic liver disease is a term that encompasses the hepatic manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with hepatic fibrosis or cirrhosis. It is the major cause of liver disease in Western countries...

.