A study published in Cell suggests that abnormal aggregation of the protein encoded by the TMEM106B gene might be a shared feature in the development of diverse neurodegenerative diseases. Researchers from the U.S., Canada and Belgium investigated post mortem human brain tissue from patients with different proteinopathies including frontotemporal lobar degeneration and progressive supranuclear palsy. Using cyroelectron microscopy and mass spectrometry, they found and analyzed fibrous aggregations of TMEM106B in these tissue samples.

Many degenerative diseases are caused by misfolded proteins which aggregate and form fibrous, insoluble structures called amyloid fibrils. This leads to the functional and structural damage and progressive loss of neurons. In this process, characteristic proteins as for example the tau protein, TDP43 or alpha-synuclein, are involved in the development of distinct neurodegenerative diseases. TMEM106B is a membrane protein and active in the transport of lysosomes and thus in the breakdown and removal of excess or old cell parts. The results of the current study indicate that fibrillization of TMEM106B might be an unknown shared mechanism underlying neurodegeneration. Further evidence of this new mechanism is provided by two other studies published at the same time in Nature.

Jiang YX, Cao Q, Sawaya MR, … Eisenberg DS. Amyloid fibrils in disease FTLD-TDP are composed of TMEM106B not TDP-43. Nature. 2022 Mar 28. doi: 10.1038/s41586-022-04670-9.

Schweighauser M, Arseni D, Bacioglu M, … Scheres SHW. Age-dependent formation of TMEM106B amyloid filaments in human brains. Nature. 2022 Mar 28. doi: 10.1038/s41586-022-04650-z.