Hyperpalmitoylated GFAP promotes astrogliosis and neurodegeneration

What is it about?

This study reports that the intermediate filament protein GFAP is modified with protein palmitoylation. Increased GFAP expression and palmitoylation is involved in astrocyte proliferation and astrogliosis. The authors demonstrate that GFAP palmitoylation is regulated by PPT1, a palmitoylprotein thioesterase linked to a childhood neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis (INCL). A palmitoylation-defective mutant of GFAP attenuates astrogliosis and the concurrent pathology in a loss-of-function PPT1 mouse. The authors conclude that accumulation of palmitoylated GFAP contributes to the pathogenesis of astrogliosis and neurodegeneration, suggesting that targeting the modified cysteine in GFAP may be a potential therapeutic strategy for the treatment of INCL and other neurodegenerative disorders.

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Photo by Clarence E. Hsu on Unsplash

Photo by Clarence E. Hsu on Unsplash

Why is it important?

Blocking GFAP palmitoylation attenuate astrogliosis, and remarkably, the concurrent neurodegenerative pathology in PPT1-deficient mice. This finding demonstrated that hyper-palmitoylated GFAP plays critical roles in regulating the pathogenesis of astrogliosis and neurodegeneration in CNS, and most importantly, pinpointing that GFAP palmitoylation might be a valuable pharmaceutical target for treating INCL and other potential neurodegenerative diseases.