Institute of Neuropathology, University Medical Center Hamburg-Eppendorf (UKE), 20251 Hamburg, Germany.
Cells. 2022 Sep 21;11(19):2948. doi: 10.3390/cells11192948.
Prion diseases are neurodegenerative diseases that affect humans and animals. They are always fatal and, to date, no treatment exists. The hallmark of prion disease pathophysiology is the misfolding of an endogenous protein, the cellular prion protein (PrP), into its disease-associated isoform PrP. Besides the aggregation and deposition of misfolded PrP, prion diseases are characterized by spongiform lesions and the activation of astrocytes and microglia. Microglia are the innate immune cells of the brain. Activated microglia and astrocytes represent a common pathological feature in neurodegenerative disorders. The role of activated microglia has already been studied in prion disease mouse models; however, it is still not fully clear how they contribute to disease progression. Moreover, the role of microglia in human prion diseases has not been thoroughly investigated thus far, and specific molecular pathways are still undetermined. Here, we review the current knowledge on the different roles of microglia in prion pathophysiology. We discuss microglia markers that are also dysregulated in other neurodegenerative diseases including microglia homeostasis markers. Data on murine and human brain tissues show that microglia are highly dysregulated in prion diseases. We highlight here that the loss of homeostatic markers may especially stand out.
朊病毒病是影响人类和动物的神经退行性疾病。它们总是致命的，迄今为止，还没有治疗方法。朊病毒病病理生理学的标志是内源性蛋白（细胞朊蛋白 PrP）错误折叠成其疾病相关的异构体 PrP。除了错误折叠的 PrP 的聚集和沉积外，朊病毒病还以海绵状病变以及星形胶质细胞和小胶质细胞的激活为特征。小胶质细胞是大脑的固有免疫细胞。激活的小胶质细胞和星形胶质细胞是神经退行性疾病的共同病理特征。激活的小胶质细胞在朊病毒病小鼠模型中的作用已经得到研究；然而，它们如何促进疾病进展仍不完全清楚。此外，小胶质细胞在人类朊病毒病中的作用迄今尚未得到彻底研究，特定的分子途径仍不确定。在这里，我们回顾了小胶质细胞在朊病毒病理生理学中不同作用的现有知识。我们讨论了也在其他神经退行性疾病中失调的小胶质细胞标记物，包括小胶质细胞稳态标记物。关于鼠脑和人脑组织的数据表明，小胶质细胞在朊病毒病中高度失调。在这里，我们强调，稳态标记物的丧失可能尤为突出。
