Aggresomes

Aggresomes are large, intracellular inclusions that form when misfolded proteins accumulate within a cell. These structures are typically found near the cell nucleus and are often associated with the microtubule organizing center. The formation of aggresomes is a cellular defense mechanism designed to sequester potentially toxic protein aggregates away from the general cytoplasm, thus protecting the cell from damage.

The process of aggresome formation involves the cell's protein degradation machinery, primarily the ubiquitin-proteasome system (UPS) and autophagy. When the UPS becomes overwhelmed with misfolded proteins, or when the proteins are too large or complex to be degraded by proteasomes, they can be channeled into aggresomes. Ubiquitin, a protein that tags other proteins for degradation, plays a crucial role in marking misfolded proteins for aggresomal targeting. These ubiquitinated proteins are then transported along microtubules to the aggresome.

While aggresomes represent an attempt by the cell to cope with protein misfolding, their formation is often linked to various diseases. Conditions such as neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease), cystic fibrosis, and certain viral infections are associated with the accumulation of misfolded proteins and the formation of aggresomes. The presence and size of aggresomes can sometimes serve as a biomarker for disease progression or cellular stress. Research into aggresome formation and degradation pathways is ongoing, with the hope of developing therapeutic strategies to alleviate diseases associated with protein misfolding.