Lysosomal dysfunction in brain health, ageing and disease with a focus on transmembrane protein 106B (TMEM106B)

Healthy brain cells use a compartment called the lysosome to recycle cellular material. Lysosomes also function as hubs for different cellular functions like defending against microbes and integrating signals within cells. We study how lysosome function impacts healthy brain ageing and neurodegeneration.

Recently, we found that a lysosomal protein called TMEM106B, changes its shape and clumps up in the brain as we age. Different versions of the TMEM106B gene have been connected to worse brain ageing in absence of diseases, but also to a high risk of developing neurodegenerative diseases such as dementias.

We are developing cell-based models of brain ageing and disease to study how lysosomal TMEM106B clumping affects brain health and its implications in disease. This approach is powerful because it will help us understand age-related changes in the brain, but also study disease mechanisms.

The growing understanding of consequences of their age-related changes in brain cells could contribute to the development of therapeutic interventions in massive neurodegeneration associated with these age-related diseases.