Abstract |
Netherton syndrome (NS) is an orphan genetic skin disease with a profound skin barrier defect and severe allergic manifestations. NS is caused by loss of function mutations in SPINK5 encoding lympho-epithelial Kazal-type inhibitor (LEKTI), a secreted multi-domain serine protease inhibitor expressed in stratified epithelia. Studies in mouse models and in NS patients have established that unopposed kallikrein 5 activity triggers stratum corneum detachment and activates PAR-2 signaling, leading to the autonomous production of pro-allergic and pro-inflammatory mediators. This emerging knowledge on NS pathogenesis has highlighted a central role for protease regulation in skin homeostasis but also in the complexity of the disease, and holds the promise of new specific treatments.
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Authors | Laetitia Furio, Alain Hovnanian |
Journal | Biological chemistry
(Biol Chem)
Vol. 395
Issue 9
Pg. 945-58
(Sep 2014)
ISSN: 1437-4315 [Electronic] Germany |
PMID | 25153381
(Publication Type: Journal Article, Review)
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Chemical References |
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Topics |
- Animals
- Disease Models, Animal
- Humans
- Hypersensitivity
(enzymology, pathology)
- Inflammation
(enzymology, pathology)
- Kallikreins
(antagonists & inhibitors, metabolism)
- Netherton Syndrome
(enzymology, pathology, therapy)
- Skin
(pathology)
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