ＡＬＳ研究会コミュのＡＬＳとアンジオジェニン

先ずは、この論文に注目しましょう。以下のアブストラクトに拠ると、
アイルランドで、７９人のＡＬＳ患者と７２人の健康な対照群の比較に
おいて、ＡＬＳ患者では血清中のアンジオジェニンが優位に上昇して
居た、と報告されて居ます。彼らは、これを診断に利用する事が出来る
のではないか、と論じて居ますが、興味深いのは、むしろ、事実ならば、
何故、ＡＬＳ患者の血清アンジオジェニンは上昇するのか？と言ふ問題
です。


Elevated serum angiogenin levels in ALS.Cronin S, Greenway MJ, Ennis S, Kieran D, Green A, Prehn JH, Hardiman O.
Department of Physiology, Royal College of Surgeons in Ireland, Ireland. scronin@rcsi.ie

BACKGROUND: The role of hypoxia responsive genes in the pathogenesis of ALS was first suggested when deletions of the hypoxia-responsive element of vascular endothelial growth factor (VEGF) promoter caused a motor neuron disease phenotype in mice. The discovery of ALS-associated mutations in ANG, a hypoxia responsive gene coding for the protein angiogenin, has further supported this pathogenic mechanism in human ALS. In endothelium, angiogenin can regulate expression of VEGF. To date, the patterns of serum angiogenin expression among patients with ALS have not been assessed. METHODS: Serum angiogenin and VEGF levels were quantified at diagnosis in 79 patients with definite or probable ALS and 72 healthy controls, using a quantitative sandwich enzyme-linked immunoassay. RESULTS: Patients with ALS exhibited higher serum angiogenin (p = 0.006) but not VEGF (p = 0.55) levels than matched control subjects. Subgroup analysis showed a greater elevation in angiogenin levels for spinal- (p < 0.001) than bulbar- (p = 0.11) onset ALS vs controls. At 12 months, angiogenin levels remained elevated. No correlation was noted between angiogenin and VEGF levels (r = -0.08, p = 0.49) in ALS patient serum. CONCLUSION: These data suggest a modest elevation in serum angiogenin in ALS at diagnosis. Further investigation will be required to assess the utility of serum angiogenin as a biomarker for ALS and as a predictor of disease progression.

PMID: 17130418 [PubMed - indexed for MEDLINE]

Greenwayらによる上の報告に対する反響です。



Another angiogenic gene linked to amyotrophic lateral sclerosis.Lambrechts D, Lafuste P, Carmeliet P, Conway EM.
The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology (VIB), KU Leuven, B-3000 Leuven, Belgium.

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.

PMID: 16843725 [PubMed - indexed for MEDLINE]