Proteotoxicity

Proteotoxicity refers to the cellular damage and dysfunction caused by the accumulation of misfolded or damaged proteins. Proteins are essential molecules that perform a vast array of functions within cells. However, during their synthesis or due to various cellular stresses, they can misfold and lose their proper three-dimensional structure. These misfolded proteins can then aggregate, forming insoluble deposits that disrupt normal cellular processes.

The mechanisms by which proteotoxicity arises are complex. Cells possess sophisticated protein quality control systems, including chaperones that assist in proper folding and proteasomes that degrade damaged proteins. When these systems are overwhelmed or compromised, misfolded proteins begin to accumulate. This accumulation can interfere with cellular machinery, leading to oxidative stress, inflammation, and ultimately cell death.

Proteotoxicity is implicated in a wide range of diseases, particularly neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. In these conditions, specific proteins aggregate in the brain, leading to neuronal dysfunction and loss. Beyond neurodegeneration, proteotoxicity is also linked to other conditions like cystic fibrosis, cancer, and aging. Research into proteotoxicity aims to understand its role in disease pathogenesis and to develop therapeutic strategies that can enhance protein quality control or clear protein aggregates.