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Toll-like receptors: potential targets for lupus treatment.

Wu YW, Tang W, Zuo JP - Acta Pharmacol. Sin. (2015)

Bottom Line: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the loss of tolerance to self-nuclear antigens.Accumulating evidence shows that Toll-like receptors (TLRs), previously proven to be critical for host defense, are implicated in the pathogenesis of autoimmune diseases by recognition of self-molecules.A number of downstream proteins in the TLR signaling cascade (such as MyD88, IRAKs and IFN-α) are identified as potential therapeutic targets for SLE treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

ABSTRACT
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the loss of tolerance to self-nuclear antigens. Accumulating evidence shows that Toll-like receptors (TLRs), previously proven to be critical for host defense, are implicated in the pathogenesis of autoimmune diseases by recognition of self-molecules. Genome-wide association studies, experimental mouse models and clinical sample studies have provided evidence for the involvement of TLRs, including TLR2/4, TLR5, TLR3 and TLR7/8/9, in SLE pathogenesis. A number of downstream proteins in the TLR signaling cascade (such as MyD88, IRAKs and IFN-α) are identified as potential therapeutic targets for SLE treatment. Numerous antagonists targeting TLR signaling, including oligonucleotides, small molecular inhibitors and antibodies, are currently under preclinical studies or clinical trials for SLE treatment. Moreover, the emerging new manipulation of TLR signaling by microRNA (miRNA) regulation shows promise for the future treatment of SLE.

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Development status of SMIs that target TLR signaling pathway for SLE treatment.
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tbl2: Development status of SMIs that target TLR signaling pathway for SLE treatment.

Mentions: Currently, there are diverse agents under development for lupus treatment by targeting TLRs or TLR accessory proteins (including MyD88, IRAK-4 and IFN-α) at different stages of TLR signaling pathways (Figure 1). Here, we focus on a series of agents in the discovery phase or in clinical trials, including oligonucleotides (Table 1), small molecular inhibitors (SMIs) (Table 2), antibodies (Table 3) and new emerging modulators, such as microRNAs, which might offer further possibilities for therapeutic manipulation.


Toll-like receptors: potential targets for lupus treatment.

Wu YW, Tang W, Zuo JP - Acta Pharmacol. Sin. (2015)

Development status of SMIs that target TLR signaling pathway for SLE treatment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4816237&req=5

tbl2: Development status of SMIs that target TLR signaling pathway for SLE treatment.
Mentions: Currently, there are diverse agents under development for lupus treatment by targeting TLRs or TLR accessory proteins (including MyD88, IRAK-4 and IFN-α) at different stages of TLR signaling pathways (Figure 1). Here, we focus on a series of agents in the discovery phase or in clinical trials, including oligonucleotides (Table 1), small molecular inhibitors (SMIs) (Table 2), antibodies (Table 3) and new emerging modulators, such as microRNAs, which might offer further possibilities for therapeutic manipulation.

Bottom Line: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the loss of tolerance to self-nuclear antigens.Accumulating evidence shows that Toll-like receptors (TLRs), previously proven to be critical for host defense, are implicated in the pathogenesis of autoimmune diseases by recognition of self-molecules.A number of downstream proteins in the TLR signaling cascade (such as MyD88, IRAKs and IFN-α) are identified as potential therapeutic targets for SLE treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

ABSTRACT
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the loss of tolerance to self-nuclear antigens. Accumulating evidence shows that Toll-like receptors (TLRs), previously proven to be critical for host defense, are implicated in the pathogenesis of autoimmune diseases by recognition of self-molecules. Genome-wide association studies, experimental mouse models and clinical sample studies have provided evidence for the involvement of TLRs, including TLR2/4, TLR5, TLR3 and TLR7/8/9, in SLE pathogenesis. A number of downstream proteins in the TLR signaling cascade (such as MyD88, IRAKs and IFN-α) are identified as potential therapeutic targets for SLE treatment. Numerous antagonists targeting TLR signaling, including oligonucleotides, small molecular inhibitors and antibodies, are currently under preclinical studies or clinical trials for SLE treatment. Moreover, the emerging new manipulation of TLR signaling by microRNA (miRNA) regulation shows promise for the future treatment of SLE.

Show MeSH
Related in: MedlinePlus