accumulation and exacerbates ADlike pathology. Furthermore, SR-B2 interacts with TLR4 and TLR6 to promote the activation of microglia by A, which induces the production of reactive oxygen species, IL-1 and other proinfl ammatory mediators as well as infl ammasome activation. These fi ndings indicate that SRs could be both benefi cial and detrimental in the progression of AD -benefi cial by promoting clearance of the neurotoxic A peptides, yet detrimental by contributing to disease progression and neurotoxicity through mediating the infl ammatory response to A. These dichotomous roles of SRs have led to their description as 'doubleedged swords'.SRs are also associated with atherosclerosis, a chronic infl ammatory disease characterized by the accumulation of modifi ed forms of lipoproteins as 'plaques' in the arterial wall. The failure of macrophages to process modifi ed lipoprotein effi ciently can lead to the formation of foam cells, thereby contributing to atherosclerosis. SR-A1, SR-A4, SR-B1, SR-B2, SR-D1, SR-E1, and SR-G1 can recognize OxLDL. Furthermore, upon exposure to modifi ed LDL, SR-B2 interacts with TLR4 and TLR6, resulting in NF-B activation and contributing to the infl ammatory response associated with atherosclerosis. The distinct role of each of these SRs in atherosclerosis is not clear; however, it is possible that the role of each SR depends on the level of its expression in a certain tissue or cell type. This interesting area of investigation remains understudied.Additionally, SRs are critically important in autoimmune diseases, such as SLE. Removal of apoptotic cells is a crucial process in immunity and in maintaining homeostasis in healthy tissues. Many cells, such as macrophages and dendritic cells, have the ability to clear apoptotic cells. A failure in the clearance of apoptotic cells can lead to their accumulation and facilitate the development of an 'anti-self' response to these cells, thereby contributing to autoimmune diseases. SLE is an example of this process, as patients with SLE have high levels of circulating apoptotic cells. SR-F1 binds to and phagocytoses apoptotic cells leading to their clearance, and, in mouse models, SR-F1 defi ciency impairs the engulfment of apoptotic cells leading to the development of a syndrome similar to SLE. Because of the limited available options to treat SLE, these fi ndings may have therapeutic implications for this disease.
ConclusionsSRs are phagocytic and innate immune recognition receptors that play a crucial role as regulators of infl ammatory signaling. These receptors are involved in multiple physiological and pathological processes, including interactions with TLRs and delivery of ligands to different cellular compartments. Additionally, the roles of these receptors in many degenerative and autoimmune diseases, as well as their potential as targets for therapeutic interventions to treat various disorders, warrant further study.