ProteostaseStörungen

ProteostaseStörungen, also known as disturbances of proteostasis, refer to disruptions in the cellular mechanisms that maintain protein homeostasis. Proteostasis encompasses protein synthesis, folding, trafficking, repair, and degradation, ensuring that functional proteins are available and damaged or misfolded proteins are removed. When these processes fail, proteins accumulate in misfolded or aggregated forms, which can impair cellular function and lead to disease.

Key mechanisms of proteostasis include chaperone-mediated folding, the ubiquitin–proteasome system, and autophagy. Stressors that can trigger proteostaseStörungen are genetic mutations that alter protein sequences, environmental toxins, oxidative stress, aging, and chronic inflammation. Viral infections can also overload cellular machinery, causing imbalances.

Clinical manifestations vary depending on the tissue affected. In neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s disease, abnormal protein aggregates form plaques or Lewy bodies. In metabolic diseases, misfolded enzymes cause enzymatic deficiencies. Cardiomyopathies, cystic fibrosis, and some cancers also exhibit proteostasis imbalance, often through misfolded transmembrane proteins or oncogenic signaling pathways.

Diagnosis involves detecting protein aggregates with histological stains, measuring chaperone activity, and assessing proteasome function. Biomarkers include circulating misfolded protein fragments, ubiquitinated proteins, and stress-induced proteins like heat shock proteins. Imaging techniques such as positron emission tomography with amyloid- or tau-binding tracers help visualize aggregates in the brain.

Therapeutic strategies focus on restoring proteostasis. Chaperone enhancers, proteasome activators, autophagy inducers, and small molecules that stabilize native protein conformations are under investigation. Gene therapy can correct underlying mutations. Lifestyle interventions such as caloric restriction, exercise, and antioxidants may also modulate proteostaseStörungen by reducing oxidative damage and enhancing autophagic flux.