Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthritis.
BACKGROUND
In the last few years, significant progress has been made in understanding the pathogenic mechanisms and in defining the role of relevant cells and molecules in the pathophysiology of rheumatoid arthritis (RA). Various therapies, both biological (anti-TNF, anti-interleukins [e.g., IL-1]) and small molecule inhibitors have been explored for the treatment of RA.


OBJECTIVE
To date, no single signaling pathway inhibitor as wide acting as the corticosteroids, is known. However, treatment with corticosteroids is also associated with allied side effects. Despite a lot of efforts in the category of small molecule inhibitors, no inhibitor is available to deal with RA at both fronts (inflammation and tissue damage), without causing immense side effects.


METHODS
This present review explores the role of spleen tyrosine kinase (Syk) in the pathogenesis of RA and also discusses how it may meet the present day therapeutic requirements for the treatment of RA. This review gives an in-depth discussion on the role of Syk signaling in RA, the possibilities of using Syk as a target and also discusses the possible side effects that could be associated with its inhibition.


CONCLUSIONS
We propose Syk inhibition as a potential therapeutic approach for the treatment of RA.
Bajpai
Malini
M
Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Plot No-20, Sector-18, Gurgaon-122001-Haryana, India. malini.bajpai@ranbaxy.com
Chopra
Puneet
P
Dastidar
Sunanda G
SG
Ray
Abhijit
A
D000818:Animals; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013154:Spleen / Q000201:enzymology* / Q000276:immunology; D000072377:Syk Kinase
D018501:Antirheumatic Agents; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase