Journal
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
Volume 51, Issue 3, Pages 249-263Publisher
SPRINGER
DOI: 10.1007/s11626-014-9832-4
Keywords
Alfy; Amyotrophic lateral sclerosis; G93A-SOD1 transgenic mouse; Cu/Zn superoxide dismutase; TDP43; Autophagy
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Autophagy-linked FYVE (Alfy) is a protein implicated in the selective degradation of aggregated proteins. In our present study, we found that Alfy was recruited into the aggregated G93A-SOD1 in transgenic mice with amyotrophic lateral sclerosis (ALS). We demonstrated that Alfy overexpression could decrease the expression of mutant proteins via the autophagosome-lysosome pathway, and thereby, the toxicity of mutant proteins was reduced. The clearance of the mutant proteins in NSC34 cells was significantly inhibited in an Alfy knockdown cellular model. We therefore deduced that Alfy translocalization likely is involved in the pathogenesis of ALS. Alfy may be developed into a useful target for ALS therapy.
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