Another angiogenic gene linked to amyotrophic lateral sclerosis.

The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology (VIB), KU Leuven, B-3000 Leuven, Belgium.
Trends in Molecular Medicine (Impact Factor: 10.11). 09/2006; 12(8):345-7. DOI: 10.1016/j.molmed.2006.06.008
Source: PubMed

ABSTRACT A new study by Greenway and colleagues links mutations in the angiogenin gene to patients with amyotrophic lateral sclerosis (ALS)--a progressive and fatal motoneuron disease. This is an unexpected finding because angiogenin was originally identified as a molecule involved in the formation of blood vessels (angiogenesis). Angiogenin bears striking similarity to vascular endothelial growth factor (VEGF), which is the prototypic angiogenic factor that has recently emerged as a molecule with important neuroprotective activities. Besides VEGF, angiogenin is the second so-called angiogenic factor implicated in ALS, raising the question of whether additional angiogenic factors might have a role in ALS. Overall, these findings identify angiogenin as a novel candidate gene in the pathogenesis of ALS--a discovery that ultimately might lead to the development of new therapeutic strategies.

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Available from: Peggy Lafuste, Aug 24, 2015
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    • "Neurovascular molecules seem to establish another mechanism in ALS (VEGF, angiogenin) and related diseases (e.g. progranulin in FTLD; Lambrechts et al., 2006). The involvement of ER stress is yet another one (SOD1, VAPB and others; Kanekura et al., 2009). "
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    ABSTRACT: Amyotrophic lateral sclerosis is a degenerative disease affecting the motor neurons. In spite of our growing insights into its biology, it remains a lethal condition. The identification of the cause of several of the familial forms of ALS allowed generation of models to study this disease both in vitro and in vivo. Here, we summarize what is known about the pathogenic mechanisms of ALS induced by hereditary mutations, and attempt to identify the relevance of these findings for understanding the pathogenic mechanisms of the sporadic form of this disease.
    European Journal of Neuroscience 06/2010; 31(12):2247-65. DOI:10.1111/j.1460-9568.2010.07260.x · 3.67 Impact Factor
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    ABSTRACT: Angiogenesis, the formation of new blood vessels, is a primordial process in development and its dysregulation has a central role in the pathogenesis of many diseases. Angiogenin (ANG), a peculiar member of the RNase A superfamily, is a potent inducer of angiogenesis involved in many different types of cancer, amyotrophic lateral sclerosis and also with a possible role in the innate immune defense. The evolutionary path of this family has been a highly dynamic one, where positive selection has played a strong role. In this work we used a combined gene and protein level approach to determine the main sites under diversifying selection on the primate ANG gene and analyze its structural and functional implications. We obtained evidence for positive selection in the primate ANG gene. Site specific analysis pointed out 15 sites under positive selection, most of which also exhibited drastic changes in amino acid properties. The mapping of these sites in the ANG 3D-structure described five clusters, four of which were located in functional regions: two in the active site region, one in the nucleolar location signal and one in the cell-binding site. Eight of the 15 sites under selection in the primate ANG gene were highly or moderately conserved in the RNase A family, suggesting a directed event and not a simple consequence of local structural or functional permissiveness. Moreover, 11 sites were exposed to the surface of the protein indicating that they may influence the interactions performed by ANG. Using a maximum likelihood gene level analysis we identified 15 sites under positive selection in the primate ANG genes, that were further corroborated through a protein level analysis of radical changes in amino acid properties. These sites mapped onto the main functional regions of the ANG protein. The fact that evidence for positive selection is present in all ANG regions required for angiogenesis may be a good indication that angiogenesis is the process under selection. However, other possibilities to be considered arise from the possible involvement of ANG in innate immunity and the potential influence or co-evolution with its interacting proteins and ligands.
    BMC Evolutionary Biology 02/2007; 7:167. DOI:10.1186/1471-2148-7-167 · 3.41 Impact Factor
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