Physiological and pathological functions of TMEM106B: a gene associated with brain aging and multiple brain disorders.
Physiological and pathological functions of TMEM106B: a gene associated with brain aging and multiple brain disorders.
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TMEM106B的生理和病理功能：一个与脑老化和多种脑疾病相关的基因。
DOI：
10.1007/s00401-020-02246-3
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发表时间：
2021-03
影响因子：
12.7
通讯作者：
Hu F
中科院分区：
文献类型：
--
作者：
Feng T;Lacrampe A;Hu F
TMEM 106 B是一种编码溶酶体膜蛋白的蛋白质，近年来被认为与脑老化、脑白质营养不良和多种神经退行性疾病有关，如额颞叶变性（FTLD）和边缘型年龄相关性TDP-43脑病（LATE）。在过去的十年中，我们对TMEM 106 B的细胞和生理功能的理解取得了相当大的进展。TMEM 106 B调节溶酶体功能的许多方面，包括溶酶体pH、溶酶体运动和溶酶体胞吐。TMEM 106 B水平的增加和减少均导致溶酶体异常。在体内，TMEM 106 B缺陷导致溶酶体运输和髓鞘形成缺陷，并在小鼠模型中增强FTLD病理学。在人类中，由TMEM 106 B多态性引起的TMEM 106 B水平的改变与神经元比例、脑老化和脑疾病密切相关。进一步阐明TMEM 106 B的生理功能和TMEM 106 B在疾病状态中的改变将产生对TMEM 106 B在脑健康和治疗与TMEM 106 B相关的脑病症的治疗开发中的作用的见解。
TMEM106B, encoding a lysosome membrane protein, has been recently associated with brain aging, hypomyelinating leukodystrophy and multiple neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). During the past decade, considerable progress has been made towards our understanding of the cellular and physiological functions of TMEM106B. TMEM106B regulates many aspects of lysosomal function, including lysosomal pH, lysosome movement and lysosome exocytosis. Both an increase and decrease in TMEM106B levels results in lysosomal abnormalities. In vivo, TMEM106B deficiency leads to lysosome trafficking and myelination defects and potentiates FTLD pathology in mouse models. In humans, alterations in TMEM106B levels caused by TMEM106B polymorphisms are intimately linked to neuronal proportions, brain aging and brain disorders. Further elucidation of the physiological function of TMEM106B and alternation of TMEM106B in the disease states will yield insights into the role of TMEM106B in brain health and therapeutic development to treat brain disorders associated with TMEM106B.
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