Mutations Impair TREM2 Maturation, Processing, and Microglial Phagocytosis

In the July 2 Science Translational Medicine, an international group of scientists reported how TREM2 missense mutations linked to neurodegenerative diseases impair the protein’s function. The mutations prevent TREM2 from reaching the cellular surface for proteolytic processing and shedding of its N-terminal into the extracellular space. Correspondingly, the scientists detected a reduction of soluble TREM2 in the CSF of patients with Alzheimer’s and frontotemporal dementia. The mutations weakened microglial phagocytosis.

Co-authors Christian Haass, Marco Colonna, and Gernot Kleinberger, as well as panelists Carlos Cruchaga, Joseph El Khoury, and Jochen Walter came together for a live discussion on July 8.

Listen to the full discussion here.

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