The role of macrophage scavenger receptor 1 (Msr1) in prion pathogenesis

Abstract

Abstract The progression of prion diseases is accompanied by the accumulation of prions in the brain. Ablation of microglia enhances prion accumulation and accelerates disease progression, suggesting that microglia play a neuroprotective role by clearing prions. However, the mechanisms underlying the phagocytosis and clearance of prion are largely unknown. The macrophage scavenger receptor 1 (Msr1) is an important phagocytic receptor expressed by microglia in the brain and is involved in the uptake and clearance of soluble amyloid-β. We therefore asked whether Msr1 might play a role in prion clearance and assessed the scavenger function of Msr1 in prion pathogenesis. We found that Msr1 expression was upregulated in prion-infected mouse brains. However, Msr1 deficiency did not change prion disease progression or lesion patterns. Prion deposition in Msr1 deficient mice was similar to their wild-type littermates. In addition, prion-induced neuroinflammation was not affected by Msr1 ablation. We conclude that Msr1 does not play a major role in prion pathogenesis. Key messages Msr1 expression is upregulated in prion-infected mouse brains at the terminal stage Msr1 deficiency does not affect prion disease progression Msr1 does not play a major role in prion clearance or prion pathogenesis Microglia-mediated phagocytosis and clearance of Aβ and prion may adopt distinct molecular pathways