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TBK1 p.E696K mutation causes autophagolysosomal dysfunction and ALS/FTD-like symptoms in mice

ABSTRACT: While deleterious mutations are responsible for the vast majority of TBK1-linked ALS/FTD cases, the ALS/FTD causing missense mutation p.E696K leads to a selective loss of TBK1/optineurin binding. Knock-in of this specific missense mutation causes progressive autophagolysosomal dysfunction and an ALS/FTD-like phenotype in mice, while, as opposed to TBK1 deletion, RIPK/TNF-α-dependent necroptosis or overt inflammation are absent. Our results highlight the role of autophagolysosomal dysfunction as a therapeutic target in TBK1-ALS/FTD.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cerebrospinal Fluid, Nerve Cord

SUBMITTER: Christian Münch

LAB HEAD: Christian Meunch

PROVIDER: PXD050731 | Pride | 2024-03-19

REPOSITORIES: Pride

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