Document Detail


Targeting angiogenin in therapy of amyotropic lateral sclerosis.
MedLine Citation:
PMID:  18781822     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: 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.
Authors:
Hiroko Kishikawa; David Wu; Guo-fu Hu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Expert opinion on therapeutic targets     Volume:  12     ISSN:  1744-7631     ISO Abbreviation:  Expert Opin. Ther. Targets     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-10     Completed Date:  2008-12-29     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  101127833     Medline TA:  Expert Opin Ther Targets     Country:  England    
Other Details:
Languages:  eng     Pagination:  1229-42     Citation Subset:  IM    
Affiliation:
Harvard Medical School, Department of Pathology, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Amyotrophic Lateral Sclerosis / drug therapy*,  genetics
Clinical Trials as Topic
Humans
RNA, Ribosomal / genetics
Ribonuclease, Pancreatic / genetics*,  physiology
Transcription, Genetic / physiology
Grant Support
ID/Acronym/Agency:
R01 CA105241/CA/NCI NIH HHS; R01 CA105241/CA/NCI NIH HHS; R01 CA105241-04/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Ribosomal; EC 3.1.27.-/angiogenin; EC 3.1.27.5/Ribonuclease, Pancreatic
Comments/Corrections

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