By G. Ying
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Additional info for Age-Related Macular Degeneration - Recent Advs. in Basic Research, Clin. Care
2008). , 2009). Similar to Mincle, the capability of CLEC9A to recognize necrotic cells makes it a potential receptor that is important for sterile inflammatory responses even though its ligands are unidentified. , 2009). NLRs contain a central nucleotide-binding oligomerization domain (NACHT), an N-terminal effector domain (pyrin domain, caspase-recruitment domain or BIR domain) and C-terminal leucine-rich repeats (LRRs). Among the NLRs identified so far, the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3, also termed as NALP3) has been shown to be capable of detecting endogenous danger signals (See discussion in NLRP3 inflammasome).
Based on their origin, DAMPs are classified into two categories: intracellular and extracellular DAMPs. 1 Intracellular DAMPs Intracellular DAMPs are bioactive mediators of intracellular origin that directly stimulate cells of the innate system. They are pre-existed within the cells and released into extracellular environment after cell injury or death. The DAMPs associated with retinal pathogenesis are summarized in Figure 1. Pathogenic Roles of Sterile Inflammation in Etiology of Age-Related Macular Degeneration 27 Fig.
SFK, src-family kinases. Syk, spleen tyrosine kinase. TAK1, transforming growth factor β–activated kinase 1. TRAF6, TNF receptor-associated factor 6. TRIF, TIR-domain-containing adapter-inducing interferon-β. , 2010). , 2011). , 2007) first promote activation of src-family kinases that trigger NF-κB- and AP-1-dependent transcription via small G-protein-MAPK pathways. Although the mechanistic details of RAGE signaling and the importance of its various ligands in disease pathology continue to be areas of investigation, activated RAGE by its various ligands also leads to activation of transcription factors NF-κB and AP-1 by ras-MAPK signaling (Glenn & Stitt, 2009).
Age-Related Macular Degeneration - Recent Advs. in Basic Research, Clin. Care by G. Ying