Nam Jeongyeon, Gwon Youngdae
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
Front Aging Neurosci. 2023 Mar 24;15:1145420. doi: 10.3389/fnagi.2023.1145420. eCollection 2023.
Biomolecular condensates are subcellular organizations where functionally related proteins and nucleic acids are assembled through liquid-liquid phase separation, allowing them to develop on a larger scale without a membrane. However, biomolecular condensates are highly vulnerable to disruptions from genetic risks and various factors inside and outside the cell and are strongly implicated in the pathogenesis of many neurodegenerative diseases. In addition to the classical view of the nucleation-polymerization process that triggers the protein aggregation from the misfolded seed, the pathologic transition of biomolecular condensates can also promote the aggregation of proteins found in the deposits of neurodegenerative diseases. Furthermore, it has been suggested that several protein or protein-RNA complexes located in the synapse and along the neuronal process are neuron-specific condensates displaying liquid-like properties. As their compositional and functional modifications play a crucial role in the context of neurodegeneration, further research is needed to fully understand the role of neuronal biomolecular condensates. In this article, we will discuss recent findings that explore the pivotal role of biomolecular condensates in the development of neuronal defects and neurodegeneration.
生物分子凝聚物是亚细胞结构，其中功能相关的蛋白质和核酸通过液-液相分离组装在一起，使其能够在没有膜的情况下大规模形成。然而，生物分子凝聚物极易受到遗传风险以及细胞内外各种因素的干扰，并且与许多神经退行性疾病的发病机制密切相关。除了经典的成核-聚合过程观点，即从错误折叠的种子触发蛋白质聚集外，生物分子凝聚物的病理转变也可促进神经退行性疾病沉积物中发现的蛋白质聚集。此外，有人提出位于突触和沿神经元突起的几种蛋白质或蛋白质-RNA复合物是具有液体样性质的神经元特异性凝聚物。由于它们的组成和功能修饰在神经退行性变的背景中起着关键作用，因此需要进一步研究以充分了解神经元生物分子凝聚物的作用。在本文中，我们将讨论最近的研究发现，这些发现探索了生物分子凝聚物在神经元缺陷和神经退行性变发展中的关键作用。
