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lüll Targeting angiogenin in therapy of amyotropic lateral sclerosis Kishikawa H; Wu D; Hu GFExpert Opin Ther Targets 2008[Oct]; 12 (10): 1229-42BACKGROUND: Missense heterozygous mutations in the coding region of angiogenin (ANG) gene, encoding a 14 kDa angiogenic RNase, were recently found in patients of amyotropic lateral sclerosis (ALS). Functional analyses have shown that these are loss-of-function mutations, implying that angiogenin deficiency is associated with ALS pathogenesis and that increasing ANG expression or angiogenin activity could be a novel approach for ALS therapy. OBJECTIVE: Review the evidence showing the involvement of angiogenin in motor neuron physiology and function, and provide a rationale for targeting angiogenin in ALS therapy. METHODS: Review the current understanding of the mechanism of angiogenin action in connection with ALS genetics, pathogenesis and therapy. CONCLUSION: ANG is the first gene whose loss-of-function mutations are associated with ALS pathogenesis. Therapeutic modulation of angiogenin level and activity in the spinal cord, either by systemic delivery of angiogenin protein or through retrograde transport of ANG-encoding viral particles, may be beneficial for ALS patients.|Amyotrophic Lateral Sclerosis/*drug therapy/genetics[MESH]|Clinical Trials as Topic[MESH]|Humans[MESH]|RNA, Ribosomal/genetics[MESH]|Ribonuclease, Pancreatic/*genetics/physiology[MESH]|Transcription, Genetic/physiology[MESH] |