Department of Chemistry, University of North Bengal, Raja Rammohanpur, Siliguri 734013, West Bengal, India.
Department of Biochemistry and Biophysics, University of Kalyani, Kalyani 741235, West Bengal, India.
Chem Commun (Camb). 2023 Dec 7;59(98):14509-14523. doi: 10.1039/d3cc04138g.
Phenylketonuria (PKU) is an inborn metabolic disorder characterized by excess accumulation of phenylalanine (Phe) and its fibril formation, resulting in progressive intellectual disability. Several research groups have approached from various directions to understand the formation of toxic amyloid fibrils from the essential amino acid Phe. Different parameters like the nature of the solvent, pH, Phe concentration, temperature, influence the fibril formation kinetics. In this article, we have summarized all major findings regarding the formation of Phe-based fibrils in aqueous and organic media and discussed how non-covalent interactions are involved in the self-assembly process using spectroscopic and microscopic techniques. The toxicity of Phe-based fibrils is compared with other neurodegenerative peptides. It is noted that the Phe-based fibrils can also induce various globular proteins into toxic fibrils. Later, we discuss the different approaches to inhibit fibril formation and reduce its toxicity. The presence of polyphenolic compounds, drugs, amino acids, nanoparticles, metal ions, crown ethers, and others showed a remarkable inhibitory effect on fibril formation. To the best of our knowledge, this is the first-ever etymological analysis of the Phe-fibrillar system and its inhibition to create a strong database against PKU.
苯丙酮尿症（PKU）是一种先天性代谢紊乱，其特征是苯丙氨酸（Phe）过量积累及其纤维形成，导致进行性智力障碍。几个研究小组从不同方向着手，试图从必需氨基酸 Phe 理解有毒淀粉样纤维的形成。不同的参数，如溶剂的性质、pH 值、Phe 浓度、温度等，都会影响纤维形成的动力学。在本文中，我们总结了有关在水相和有机相中介导 Phe 形成纤维的所有主要发现，并讨论了非共价相互作用如何通过光谱和显微镜技术参与自组装过程。还比较了基于 Phe 的纤维与其他神经退行性肽的毒性。值得注意的是，基于 Phe 的纤维也可以诱导各种球状蛋白形成毒性纤维。之后，我们讨论了抑制纤维形成和降低其毒性的不同方法。多酚化合物、药物、氨基酸、纳米粒子、金属离子、冠醚等的存在对纤维形成表现出显著的抑制作用。据我们所知，这是对 Phe 纤维系统及其抑制作用进行词源学分析以创建针对 PKU 的强大数据库的首次尝试。
