Increased TMEM106B levels lead to lysosomal dysfunction which affects synaptic signaling and neuronal health.

ABSTRACT:

Background

Genetic variation in Transmembrane protein 106B (TMEM106B) is known to influence the risk and presentation in several neurodegenerative diseases and modifies healthy aging. While evidence from human studies suggests that the risk allele is associated with higher levels of TMEM106B, the contribution of elevated levels of TMEM106B to neurodegeneration and aging has not been assessed and it remains unclear how TMEM106B modulates disease risk.

Methods

To study the effect of increased TMEM106B levels, we generated Cre-inducible transgenic mice expressing human wild-type TMEM106B. We evaluated lysosomal and neuronal health using in vitro and in vivo assays including transmission electron microscopy, immunostainings, behavioral testing, electrophysiology, and bulk RNA se

SUBMITTER: Perneel J 

PROVIDER: S-EPMC12016085 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature