Journal article
Noxa in rheumatic diseases: present understanding and future impact
Rheumatology (Oxford, England), Vol.53(9), pp.1539-1546
09/2014
Handle:
https://hdl.handle.net/2376/115862
PMCID: PMC4135581
PMID: 24352336
Abstract
Impaired programmed cell death is an important contributing mechanism in the development of chronic inflammatory and autoimmune diseases. Overexpression of Bcl-2 family proteins in such diseases has led to the concept of targeted suppression of these proteins as a primary therapeutic strategy. However, limited success with this approach has prompted pharmacologists to look at the other side of the coin, with the aim of reactivating jeopardized pro-apoptotic proteins that may neutralize Bcl-2 or other anti-apoptotic molecules. In this effort, BH3-only proteins have gained recent attention as endogenous molecules for the sensitization of resistant cells to undergo apoptosis. Among the BH3-only family, Noxa stands out as exceptional for its specificity to bind Mcl-1 and Bcl-2 and blunt their biological properties. Noxa is now being tested as a promising therapeutic target in cancer biology. Nonetheless, its role and clinical application still lack validation in autoimmune diseases, including rheumatic conditions. This is partly attributed to the significant gap in our understanding of its regulatory role and how either overexpression of Noxa or delivery of BH3 mimetics could be therapeutically exploited. In this review we highlight some recent studies in RA, OA, SLE and SS suggesting that Noxa may be used as a potential therapeutic target to circumvent invasive and tissue destructive processes in these rheumatic diseases.
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Details
- Title
- Noxa in rheumatic diseases: present understanding and future impact
- Creators
- Karissa E Cottier - Department of Pharmacology, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH and Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USAElise M Fogle - Department of Pharmacology, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH and Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USADavid A Fox - Department of Pharmacology, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH and Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USASalahuddin Ahmed - Department of Pharmacology, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH and Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA. Salah.Ahmed@utoledo.edu
- Publication Details
- Rheumatology (Oxford, England), Vol.53(9), pp.1539-1546
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- England
- Grant note
- R03 AR055741 / NIAMS NIH HHS R01 AR063104 / NIAMS NIH HHS AR-055741 / NIAMS NIH HHS R01 AR-063104 / NIAMS NIH HHS
- Identifiers
- 99900547415101842
- Language
- English
- Resource Type
- Journal article