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

Eur. Respir. J. 40, 1260-1268 (2012)
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The proteasome constitutes the main protein waste disposal and recycling system of the cell. Together with the endoplasmatic reticulum (ER) stress and the autophagosome pathway, it also takes centre stage in cellular protein quality control. In lung research, the proteasome is - first of all - a promising therapeutic target to intervene with 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 regulator contributes to loss of function of lung epithelial cells. In chronic obstructive pulmonary disease (COPD), pulmonary proteasome expression and activity is downregulated and inversely correlates with lung function. In addition, as the proteasome degrades signaling 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 aging. 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter proteasome; lung cancer; asthma; pulmonary fibrosis; cystic fibrosis; asthma; lung disease
ISSN (print) / ISBN 0903-1936
e-ISSN 1399-3003
Quellenangaben Band: 40, Heft: 5, Seiten: 1260-1268 Artikelnummer: , Supplement: ,
Verlag European Respiratory Society
Verlagsort Sheffield
Begutachtungsstatus Peer reviewed