Mechanism-based therapeutic targets of pemphigus vulgaris: A scoping review of pathogenic molecular pathways.
acantholysis
caspases
kinases
molecular pathways
pemphigus vulgaris
Journal
Experimental dermatology
ISSN: 1600-0625
Titre abrégé: Exp Dermatol
Pays: Denmark
ID NLM: 9301549
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
20
07
2021
received:
13
05
2021
accepted:
19
08
2021
pubmed:
27
8
2021
medline:
22
4
2022
entrez:
26
8
2021
Statut:
ppublish
Résumé
Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterised by cell-cell detachment or acantholysis. The mechanisms which follow antibody (Ab) binding and culminate in acantholytic changes and skin/mucosal blistering have not been fully clarified. Current treatment strategies are not specific to PV pathophysiology and although life-saving, harbour considerable side effects. We aimed to systematically assess the molecules amenable to targeted treatments that follow Ab binding and are associated with PV acantholysis. The resulting scoping review was conducted under PRISMA-ScR guidelines with clear inclusion and exclusion criteria and focused specifically on kinases, caspases, proteases, hydrolytic enzymes and other molecules of interest postulated to take part in the pathophysiology of PV. The review process resulted in the identification of 882 articles, of which 56 were eligible for qualitative synthesis. From the included articles, the majority (n = 42) used PV-IgG as the pathogenic agent, mainly via in vitro (n = 16) and in vivo (n = 10) models. Twenty-five molecules were found to play a pathogenic role in PV, including uPA, ADAM10, EGFR, Src, PKC, cdk2, ERK, PLC, calmodulin, NOS, p38MAPK and caspase-3. Selective inhibition of these molecules resulted in varying degrees of reduction in acantholysis and blistering. The pathogenic molecules identified in this review represent potential candidates for clinical translation.
Substances chimiques
Autoantibodies
0
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
154-171Informations de copyright
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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