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Acta Neuropathologica
Published in: Acta Neuropathologica 5/2016

01-11-2016 | Review

What we know about TMEM106B in neurodegeneration

Authors: Alexandra M. Nicholson, Rosa Rademakers

Published in: Acta Neuropathologica | Issue 5/2016

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Abstract

Frontotemporal lobar degeneration is a neurodegenerative disorder affecting over 50,000 people in the United States alone. The most common pathological subtype of FTLD is the presence of ubiquitinated TAR DNA binding protein 43 (TDP-43) accumulations in frontal and temporal brain regions at autopsy. While some cases of FTLD-TDP can be attributed to the inheritance of disease-causing mutations, the majority of cases arise with no known genetic cause. In 2010, the first genome-wide association study was conducted in patients with FTLD-TDP to determine potential genetic risk factors for this homogenous subgroup of dementia patients, leading to the identification of the TMEM106B locus on chromosome 7. In this manuscript, we review the initial discovery and replication studies describing TMEM106B variants as disease risk factors and modifiers in TDP-43 proteinopathies, such as FTLD-TDP caused by progranulin (GRN) or chromosome 9 open reading frame 72 (C9orf72) mutations, as well as Alzheimer’s disease and hippocampal sclerosis. We further summarize what is currently known about the previously uncharacterized TMEM106B protein and its role as a potential regulator of lysosomal function, and we discuss how modifying TMEM106B levels might uncover promising therapeutic strategies for individuals suffering from TDP-43 proteinopathy.
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Metadata
Title
What we know about TMEM106B in neurodegeneration
Authors
Alexandra M. Nicholson
Rosa Rademakers
Publication date
01-11-2016
Publisher
Springer Berlin Heidelberg
Published in
Acta Neuropathologica / Issue 5/2016
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-016-1610-9

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