School of Basic Medical Sciences, Fudan University, Dong'An Road 130, Shanghai, 200032, China.
Institute of Neuropathology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland.
J Mol Med (Berl). 2021 Jun;99(6):877-887. doi: 10.1007/s00109-021-02061-7. Epub 2021 Mar 23.
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.
朊病毒病的进展伴随着朊病毒在大脑中的积累。小胶质细胞的消融增强了朊病毒的积累并加速了疾病的进展，这表明小胶质细胞通过清除朊病毒发挥神经保护作用。然而，朊病毒吞噬和清除的机制在很大程度上尚不清楚。巨噬细胞清道夫受体 1（Msr1）是大脑中小胶质细胞表达的一种重要吞噬受体，参与可溶性淀粉样蛋白-β的摄取和清除。因此，我们询问 Msr1 是否可能在朊病毒清除中发挥作用，并评估了 Msr1 在朊病毒发病机制中的吞噬功能。我们发现，Msr1 在朊病毒感染的小鼠大脑中的表达上调。然而，Msr1 缺失并没有改变朊病毒病的进展或病变模式。Msr1 缺陷小鼠中的朊病毒沉积与野生型同窝仔相似。此外，朊病毒诱导的神经炎症不受 Msr1 消融的影响。我们的结论是，Msr1 在朊病毒发病机制中不起主要作用。关键信息：在朊病毒感染的小鼠大脑的终末期，Msr1 的表达上调 Msr1 缺失不影响朊病毒病的进展 Msr1 对朊病毒的清除或朊病毒发病机制没有重要作用 小胶质细胞介导的 Aβ 和朊病毒的吞噬和清除可能采用不同的分子途径。
