Autophagy-linked FYVE protein (Alfy) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS).

Abstract	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.
Authors	Huihui Han, Wanyi Wei, Weisong Duan, Yansu Guo, Yi Li, Jie Wang, Yue Bi, Chunyan Li
Journal	In vitro cellular & developmental biology. Animal (In Vitro Cell Dev Biol Anim) Vol. 51 Issue 3 Pg. 249-63 (Mar 2015) ISSN: 1543-706X [Electronic] Germany
PMID	25385288 (Publication Type: Journal Article)
Chemical References	Adaptor Proteins, Signal Transducing Autophagy-Related Proteins DNA-Binding Proteins Mutant Proteins Protein Aggregates Proteins Vesicular Transport Proteins Wdfy3 protein, mouse Superoxide Dismutase
Topics	Adaptor Proteins, Signal Transducing Amyotrophic Lateral Sclerosis (metabolism, pathology) Animals Astrocytes (metabolism) Autophagy Autophagy-Related Proteins Cell Nucleus (metabolism) Cytoprotection DNA-Binding Proteins (metabolism, toxicity) Disease Models, Animal Female Gene Knockdown Techniques Humans Intracellular Space (metabolism) Lumbar Vertebrae (metabolism, pathology) Lysosomes (metabolism) Mice, Transgenic Microglia (metabolism) Motor Neurons (metabolism, pathology) Mutant Proteins (metabolism) Phagosomes (metabolism) Protein Aggregates Protein Folding Protein Transport Proteins (metabolism) Superoxide Dismutase (metabolism) Transfection Vesicular Transport Proteins (metabolism)

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