Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, 345 Weill Hall, Ithaca, NY, 14853, USA.
Acta Neuropathol. 2021 Mar;141(3):327-339. doi: 10.1007/s00401-020-02246-3. Epub 2021 Jan 1.
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 result in lysosomal abnormalities. In mouse models, TMEM106B deficiency leads to lysosome trafficking and myelination defects and FTLD related pathology. In humans, alterations in TMEM106B levels or function are intimately linked to neuronal proportions, brain aging, and brain disorders. Further elucidation of the physiological function of TMEM106B and changes in TMEM106B under pathological conditions will facilitate therapeutic development to treat brain disorders associated with TMEM106B.
TMEM106B 编码溶酶体膜蛋白，最近与大脑衰老、脱髓鞘性白质营养不良和多种神经退行性疾病相关，如额颞叶痴呆（FTLD）和边缘为主的年龄相关性 TDP-43 脑病（LATE）。在过去的十年中，我们对 TMEM106B 的细胞和生理功能有了相当多的了解。TMEM106B 调节溶酶体功能的许多方面，包括溶酶体 pH 值、溶酶体运动和溶酶体胞吐作用。TMEM106B 水平的增加和减少都会导致溶酶体异常。在小鼠模型中，TMEM106B 缺乏导致溶酶体运输和髓鞘形成缺陷以及与 FTLD 相关的病理学。在人类中，TMEM106B 水平或功能的改变与神经元比例、大脑衰老和大脑疾病密切相关。进一步阐明 TMEM106B 的生理功能以及在病理条件下 TMEM106B 的变化将有助于治疗与 TMEM106B 相关的大脑疾病的治疗方法的开发。
