V-ATP酶在神经系统中的生物学作用

Biological Effects of V-ATPase in the Nervous System

V-ATP酶是一种依靠水解ATP提供能量来转移质子的多亚基H+转运酶,主要分布于真核细胞内多种细胞器的内膜系统上,在人体的肾、脑、睾丸、内耳、骨骼、皮肤等器官有广泛表达。包括肾小管酸中毒、骨硬化症、神经性听力损失和肿瘤转移等多种人类疾病都与V-ATP酶功能有关。V-ATP酶功能异常可诱发多器官病变,如耳聋-甲发育不全综合征,其主要表型包括感音神经性耳聋、指/趾甲发育不良、锥形牙齿、指骨发育不良、学习记忆障碍等。此外,近期研究发现V-ATP酶与帕金森和阿尔兹海默症等多种神经系统退行性病变密切相关。本文将对V-ATP酶在神经系统的生物学作用进行综述。

V-ATPase is a muti-subunit H+ transporter that relies on the hydrolysis of ATP to transfer protons,andis mainly distributed in the endometrium of many organelles in eukaryotic cells. In humans, V-ATPase expresses extensivelyin various organs like the kidney, brain, testis, inner ear and bone. Many human diseases such as renal tubular acidosis,osteopetrosis, sensorineural hearing loss and tumor metastasis involves pathological function changes ofV-ATPase. V-ATPase abnormality can cause multiple phenotypes involving different organs. Dominant deafness-onychodystrophy(DDOD) syndrome is characteristic of congenital deafness, absent nails and/or toes with variable presenceof brachydactyly, pointed teeth, bulbous distal phalanges, and learning and memory disorders. Recent researches haveshown that abnormalities in V-ATPase lead to degenerative changes in peripheral and central nervous systems, with typicalphenotypes such as Parkinsin's disease and Alzheimer’s disease. This review summarizes the biological roles ofV-ATPase in the nervous system.