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Eur Respir J. 2012 Nov;40(5):1260-8. doi: 10.1183/09031936.00208511. Epub 2012 Mar 22.

What shall we do with the damaged proteins in lung disease? Ask the proteasome!

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University Hospital, Ludwig Maximilians University and Helmholtz Zentrum M√ľnchen, Munich, Germany.


The proteasome constitutes the main protein waste disposal and recycling system of the cell. Together with endoplasmic reticulum stress and the autophagosome pathway, it takes centre stage in cellular protein quality control. In lung research, the proteasome is, first of all, a promising therapeutic target to intervene in the malignant growth of lung cancer cells. Therapeutic targeting of the proteasome has also been extended to pulmonary fibrosis and asthma using animal models. Moreover, the proteasome is involved in lung pathogenesis. In cystic fibrosis, rapid proteasomal degradation of mutant cystic fibrosis transmembrane conductance regulator contributes to loss of function of lung epithelial cells. In chronic obstructive pulmonary disease (COPD), pulmonary proteasome expression and activity are downregulated and inversely correlate with lung function. In addition, as the proteasome degrades signalling mediators that have been oxidatively modified in COPD, it contributes to further compromise cellular function. The consequences of proteasomal dysfunction are loss of protein quality control, accumulation of misfolded proteins and exacerbation of cellular stress, which are also hallmarks of protein quality diseases and premature ageing. This suggests that proteasome dysfunction can be regarded as a new pathomechanism for chronic lung diseases, awaiting further therapeutic exploration in the future.

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