What is the Origin of Loss of Proteostasis?

The term stems from molecular biology and the study of cellular quality control mechanisms, with the concept of "proteostasis" formally established to describe the dynamic equilibrium of the proteome. Its relevance to clinical endocrinology lies in the fact that many hormone receptors and signaling molecules are proteins highly susceptible to misfolding and degradation.

What is the Mechanism of Loss of Proteostasis?

This loss is primarily driven by age-related decline in key cellular systems, including the chaperone network, which assists protein folding, the ubiquitin-proteasome system, which degrades short-lived proteins, and the autophagy-lysosome pathway, which clears aggregated proteins and organelles. When these systems fail, misfolded proteins accumulate, causing endoplasmic reticulum stress and cellular toxicity. This accumulation directly impairs the synthesis and function of peptide hormones and cell-surface receptors.

Loss of Proteostasis

Meaning

Loss of Proteostasis, or impaired proteome homeostasis, is the fundamental cellular pathology characterized by a failure in the complex, interconnected processes that regulate the synthesis, folding, trafficking, and degradation of proteins. This cellular dysfunction leads to the accumulation of misfolded, aggregated, and toxic proteins, significantly impairing cellular function and hormonal signaling across all tissues. It is a major hallmark of cellular aging and chronic degenerative disease.