aggresomal

Aggresomes are discrete, highly organized cytoplasmic inclusions that form in response to the accumulation of misfolded or damaged proteins. These structures are typically found near the nucleus and are characterized by a dense core surrounded by a proteinaceous shell. The formation of aggresomes is a cellular defense mechanism aimed at sequestering potentially toxic protein aggregates, thereby preventing their spread and damage to cellular functions.

The process of aggresome formation is often linked to the ubiquitin-proteasome system (UPS) and autophagy, two major cellular pathways responsible for protein degradation. When the UPS becomes overwhelmed by the sheer volume of misfolded proteins, or when it is impaired, these proteins can begin to aggregate. Chaperone proteins, which assist in protein folding, can play a role in recognizing and directing these misfolded proteins towards aggresome formation.

Upon formation, aggresomes can act as a temporary holding site for these aggregates. In some cases, the cellular machinery may eventually clear the aggresome contents through autophagy, a process where cellular components are degraded within lysosomes. However, persistent aggresome formation can also be associated with various cellular dysfunctions and diseases.

Aggresomes have been implicated in the pathogenesis of several neurodegenerative diseases, including Huntington's disease, Alzheimer's disease, and Parkinson's disease, where the accumulation of specific misfolded proteins is a hallmark. Research into aggresomes continues to explore their precise role in cellular homeostasis and their potential as therapeutic targets for proteinopathies.