Department of Neuropathology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Int J Mol Sci. 2022 Jun 2;23(11):6227. doi: 10.3390/ijms23116227.
The idea that a common pathology underlies various neurodegenerative diseases and dementias has attracted considerable attention in the basic and medical sciences. Polyglutamine binding protein-1 (PQBP1) was identified in 1998 after a molecule was predicted to bind to polyglutamine tract amino acid sequences, which are associated with a family of neurodegenerative disorders called polyglutamine diseases. Hereditary gene mutations of cause intellectual disability, whereas acquired loss of function of PQBP1 contributes to dementia pathology. PQBP1 functions in innate immune cells as an intracellular receptor that recognizes pathogens and neurodegenerative proteins. It is an intrinsically disordered protein that generates intracellular foci, similar to other neurodegenerative disease proteins such as TDP43, FUS, and hnRNPs. The knowledge accumulated over more than 20 years has given rise to a new concept that shifts in the equilibrium between physiological and pathological processes have their basis in the dysregulation of common protein structure-linked molecular mechanisms.
一种观点认为，多种神经退行性疾病和痴呆症的共同发病机制引起了基础和医学科学界的广泛关注。1998 年，一种被预测能与多聚谷氨酰胺序列氨基酸结合的分子被鉴定出来，随后发现它与一类被称为多聚谷氨酰胺疾病的神经退行性疾病有关，这种蛋白被称为多聚谷氨酰胺结合蛋白-1（PQBP1）。引起智力障碍的是 的遗传性基因突变，而 PQBP1 的获得性功能丧失则导致痴呆症的病理变化。在先天免疫细胞中，PQBP1 作为一种细胞内受体，能识别病原体和神经退行性蛋白。它是一种无序蛋白，能形成细胞内焦点，与 TDP43、FUS 和 hnRNPs 等其他神经退行性疾病蛋白类似。20 多年来积累的知识产生了一个新概念，即生理和病理过程之间平衡的转变，其基础是共同的蛋白质结构连接的分子机制的失调。
