Data from: Prion protein inhibits fast axonal transport through a mechanism involving casein kinase 2

Prion diseases include a number of progressive neuropathies involving conformational changes in cellular prion protein (PrPc) that may be fatal sporadic, familial or infectious. Pathological evidence indicated that neurons affected in prion diseases follow a dying-back pattern of degeneration. However, specific cellular processes affected by PrPc that explain such a pattern have not yet been identified. Results from cell biological and pharmacological experiments in isolated squid axoplasm and primary cultured neurons reveal inhibition of fast axonal transport (FAT) as a novel toxic effect elicited by PrPc. Pharmacological, biochemical and cell biological experiments further indicate this toxic effect involves casein kinase 2 (CK2) activation, providing a molecular basis for the toxic effect of PrPc on FAT. CK2 was found to phosphorylate and inhibit light chain subunits of the major motor protein conventional kinesin. Collectively, these findings suggest CK2 as a novel therapeutic target to prevent the gradual loss of neuronal connectivity that characterizes prion diseases.朊病毒疾病是一类涉及细胞型朊蛋白（cellular prion protein, PrPc）构象改变的进行性神经病变，可表现为致死性散发性、家族性或传染性三种亚型。病理证据表明，受该疾病累及的神经元遵循逆行性变性模式。然而，PrPc介导此类变性模式的具体细胞过程迄今尚未明确。通过对分离鱿鱼轴浆及原代培养神经元开展的细胞生物学与药理学实验，研究团队发现PrPc可诱发快速轴浆运输（fast axonal transport, FAT）抑制这一新型毒性效应。进一步的药理学、生物化学与细胞生物学实验证实，该毒性效应依赖酪蛋白激酶2（casein kinase 2, CK2）的激活，为PrPc对FAT的毒性作用提供了分子基础。研究发现CK2可磷酸化并抑制主要运动蛋白常规驱动蛋白（conventional kinesin）的轻链亚基。综上，上述研究结果提示CK2可作为新型治疗靶点，用于阻断朊病毒疾病特征性的神经元连接进行性丧失。