Neurology Department, Experimental Research in Stroke and Inflammation (ERSI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Cells. 2020 Jul 2;9(7):1609. doi: 10.3390/cells9071609.
Ischemic stroke belongs to the leading causes of mortality and disability worldwide. Although treatments for the acute phase of stroke are available, not all patients are eligible. There is a need to search for therapeutic options to promote neurological recovery after stroke. The cellular prion protein (PrPC) has been consistently linked to a neuroprotective role after ischemic damage: it is upregulated in the penumbra area following stroke in humans, and animal models of stroke have shown that lack of PrPC aggravates the ischemic damage and lessens the functional outcome. Mechanistically, these effects can be linked to numerous functions attributed to PrPC: (1) as a signaling partner of the PI3K/Akt and MAPK pathways, (2) as a regulator of glutamate receptors, and (3) promoting stem cell homing mechanisms, leading to angio- and neurogenesis. PrPC can be cleaved at different sites and the proteolytic fragments can account for the manifold functions. Moreover, PrPC is present on extracellular vesicles (EVs), released membrane particles originating from all types of cells that have drawn attention as potential therapeutic tools in stroke and many other diseases. Thus, identification of the many mechanisms underlying PrPC-induced neuroprotection will not only provide further understanding of the physiological functions of PrPC but also new ideas for possible treatment options after ischemic stroke.
缺血性中风属于全球范围内导致死亡和残疾的主要原因之一。尽管有治疗中风急性期的方法，但并非所有患者都适用。因此，需要寻找治疗选择，以促进中风后的神经功能恢复。细胞朊病毒蛋白（PrPC）一直与缺血性损伤后的神经保护作用有关：在人类中风后的半影区中，其表达上调，中风动物模型表明缺乏 PrPC 会加重缺血性损伤并降低功能预后。从机制上讲，这些作用可以与 PrPC 所具有的多种功能联系起来：（1）作为 PI3K/Akt 和 MAPK 途径的信号伴侣，（2）作为谷氨酸受体的调节剂，以及（3）促进干细胞归巢机制，从而促进血管生成和神经发生。PrPC 可以在不同的部位被切割，而蛋白酶解片段可以解释其多种功能。此外，PrPC 存在于细胞外囊泡（EVs）中，EVs 是源自所有类型细胞的膜颗粒，它们作为中风和许多其他疾病的潜在治疗工具引起了人们的关注。因此，鉴定 PrPC 诱导的神经保护作用的许多机制不仅将提供对 PrPC 生理功能的进一步理解，而且还为缺血性中风后可能的治疗选择提供了新的思路。
