Physiological and Pathological Functions of TMEM106B: a Gene Associated with Brain Aging and Multiple Brain Disorders

Overview

Journal Acta Neuropathol

Specialty Neurology

Date 2021 Jan 2

PMID 33386471

Citations 43

Authors

Tuancheng Feng

Alexander Lacrampe

Fenghua Hu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

TMEM106B deficiency leads to alterations in lipid metabolism and obesity in the TDP-43 knock-in mouse model.

Yang C, Lee G, Hao L, Hu F Commun Biol. 2025; 8(1):315.

PMID: 40011708 PMC: 11865606. DOI: 10.1038/s42003-025-07752-2.

Tracing TMEM106B fibril deposition in aging and Parkinson's disease with dementia brains.

Zhao W, Fan Y, Zhao Q, Fan Z, Zhao J, Yu W Life Med. 2025; 3(1):lnae011.

PMID: 39872397 PMC: 11749594. DOI: 10.1093/lifemedi/lnae011.

TMEM106B C-terminal fragments aggregate and drive neurodegenerative proteinopathy in transgenic Caenorhabditis elegans.

Riordan R, Saxton A, Han M, McMillan P, Kow R, Liachko N Alzheimers Dement. 2024; 21(2):e14468.

PMID: 39711302 PMC: 11848199. DOI: 10.1002/alz.14468.

Two novel variants in GRN: the relevance of CNV analysis and genetic screening in FTLD patients with a negative family history.

De Houwer J, Dopper E, Rajicic A, van Buuren R, Arcaro M, Galimberti D J Neurol. 2024; 272(1):64.

PMID: 39680222 PMC: 11649753. DOI: 10.1007/s00415-024-12758-7.

Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease.

Du M, Akerman S, Fare C, Ruan L, Vidensky S, Mamedova L Res Sq. 2024; .

PMID: 39606446 PMC: 11601866. DOI: 10.21203/rs.3.rs-5306005/v1.

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