Autophagy-linked FYVE protein (Alfy) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS).
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.
Department of Neurology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
Huihui
H
Han
Wanyi
W
Wei
Weisong
W
Duan
Yansu
Y
Guo
Yi
Y
Li
Jie
J
Wang
Yue
Y
Bi
Chunyan
C
Li
D048868:Adaptor Proteins, Signal Transducing; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D002467:Cell Nucleus / Q000378:metabolism; D019610:Cytoprotection; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D050505:Mutant Proteins / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D066329:Protein Aggregates; D017510:Protein Folding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D004268:DNA-Binding Proteins; D050505:Mutant Proteins; D066329:Protein Aggregates; D011506:Proteins; D033921:Vesicular Transport Proteins; C496370:Wdfy3 protein, mouse; D013482:Superoxide Dismutase