
-   SR-A is upregulated in microglia associated with amyloid deposits in brains of patients with Alzheimer's disease [PMID: 8579103]. MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-kappaB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons [PMID: 32066456]. SR-A on murine peritoneal macrophages has been implicated in the clearance of myelin debris and apoptotic thymocytes [PMID: 8901603, PMID: 9517470].
-   Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL) [PMID: 9069289]. JNK2-dependent phosphorylation of SR-A promotes uptake of lipids in macrophages, thereby regulating foam cell formation, a critical step in atherogenesis [PMID: 15567863].
-   In the CNS, SR-A on neonatal microglia mediates the binding and phagocytosis of apoptotic cells that express phosphatidylserine [PMID: 1545126, PMID: 8867846]. SR-A mediates adhesion and endocytosis of fibrillar beta-amyloid by microglia and that SR-A participates in secretion of reactive oxygen species by microglia, suggest its roles in neuropathology [PMID: 11240025, PMID: 15987691].

## Summary

The Msr1 gene encodes macrophage scavenger receptor 1 (MSR1) proteins, which are integral membrane glycoproteins involved in the endocytosis of modified low-density lipoproteins (LDL), the regulation of lipid homeostasis, and the immune response to pathogens and cell debris [CS: 9]. MSR1 function includes the phagocytosis of myelin debris and apoptotic cells, contributing to clearance and inflammatory response through NF-kappaB signaling [CS: 9]. In the brain, MSR1-mediated clearance of apoptotic cells and amyloid aggregates is critical due to the organ's limited regenerative capacity and sensitivity to inflammatory damage [CS: 8].

In the context of neurodegenerative diseases like Alzheimer's disease (AD), Msr1 expression is upregulated in microglia, the brain's resident immune cells [CS: 8]. This upregulation leads to enhanced binding and phagocytosis of fibrillar beta-amyloid by microglia, a process potentially aimed at clearing amyloid plaques and mitigating their toxic impact on neural tissues [CS: 7]. Similarly, it manages the clearance of myelin debris, which could otherwise trigger chronic inflammation and damage to neurons [CS: 7]. The increase in Msr1 expression following exposure to brain insults, such as ischemia, hypoxia, or administration of pro-inflammatory agents like LPS, can be viewed as an acute response facilitating the removal of pathogenic or damaged material and aimed at restoring homeostasis [CS: 9]. This response involves the NF-kappaB pathway, enhancing the release of inflammatory mediators for the defense against pathogens and promoting apoptosis of damaged cells, which MSR1-marked microglia then phagocytose to maintain tissue health [CS: 8].
