Gavín Rosalina, Del Río José Antonio
Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Avinguda Diagonal 643, 08028, Barcelona, Spain.
Molecular and Cellular Neurobiotechnology, Institute for Bioengineering of Catalonia, Baldiri and Reixac, 15-21, 08028, Barcelona, Spain.
Mol Neurobiol. 2025 Jun 28. doi: 10.1007/s12035-025-05163-2.
Cellular prion protein (PrP) and tau are highly expressed in the brain and overlap at the cellular level in neurons. Both proteins contribute directly to neurodegeneration processes in a misfolding state, although in their natural conformation, they play important roles in neurogenesis that could have a common link according to the recent literature. In this sense, it is well known that the proteinase-K resistant PrP isoform (PrP), the prion, is the causal agent of prionopathies. And misfolded tau, which is responsible for tauopathies, is considered "prion-like" because it displays similar behavior to prions in terms of self-aggregation and spreading properties. At the physiological level, PrP potentiates neuronal differentiation while tau intervenes in axonal maturation and elongation. Likewise, recent studies from our laboratory reported that PrP directly affects the alternative splicing of tau through inhibition of GSK3β while tau, in turn, can regulate PRNP transcription. In this review, we first describe the biology and physiological roles of PrP and tau in the central nervous system (CNS). Second, in the effort to improve our understanding of a possible cooperation between them in various cellular circumstances, we also discuss the molecular convergence points between PrP and tau in neurodegeneration and in natural neuronal physiology.
细胞朊蛋白（PrP）和tau蛋白在大脑中高度表达，且在神经元的细胞水平上存在重叠。尽管在其天然构象中，这两种蛋白质在神经发生中发挥着重要作用，根据最近的文献，它们可能存在共同联系，但在错误折叠状态下，它们都直接导致神经退行性变过程。从这个意义上说，众所周知，蛋白酶K抗性PrP异构体（PrP），即朊病毒，是朊病毒病的病原体。而导致tau蛋白病的错误折叠的tau蛋白被认为是“类朊病毒”，因为它在自我聚集和传播特性方面表现出与朊病毒相似的行为。在生理水平上，PrP增强神经元分化，而tau蛋白参与轴突成熟和延长。同样，我们实验室最近的研究报告称，PrP通过抑制GSK3β直接影响tau蛋白的可变剪接，而tau蛋白反过来可以调节PRNP转录。在这篇综述中，我们首先描述PrP和tau蛋白在中枢神经系统（CNS）中的生物学和生理作用。其次，为了更好地理解它们在各种细胞环境中可能的协同作用，我们还讨论了PrP和tau蛋白在神经退行性变和自然神经元生理学中的分子交汇点。
