Open AccessPhysiological and pathological functions of TMEM106B: a gene associated with brain aging and multiple brain disorders
Author(s) -
Tuancheng Feng,
Alexander Lacrampe,
Fenghua Hu
Publication year - 2021
Publication title -
acta neuropathologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.183
H-Index - 170
eISSN - 1432-0533
pISSN - 0001-6322
DOI - 10.1007/s00401-020-02246-3
Subject(s) - lysosome , frontotemporal lobar degeneration , neuroscience , endosome , tauopathy , biology , frontotemporal dementia , medicine , microbiology and biotechnology , neurodegeneration , pathology , dementia , disease , biochemistry , intracellular , enzyme
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.