ANG
angiogenin
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.
Pathology
susceptibility to amyotrophic lateral sclerosis (ALS) (MIM.105400)
Mutations in ANG have been linked to ALS, emphasizing a potential link between altered angiogenesis and motor neuron degeneration.
Seven missense mutations were identified in 15 patients with familial ALS and 11 apparently sporadic ALS patients. ANG mutations segregate with familial and ‘sporadic’ amyotrophic lateral sclerosis.However, these mutations seem restricted to Irish and Scottish populations, as they were not found in English, Swedish, and North American populations and therefore suggest that ALS-linked ANG mutations are rare.
The manner in which the identified mutations affect angiogenin function and provoke motor neuron disease is still unknown.
Angiogenin, which is expressed within the CNS including the motor neurons, has a known intranuclear RNase activity that can facilitate rRNA synthesis, at least in endothelial cells.
Interestingly, the majority of the mutations found in ALS patients are located within the catalytic core, and one of them is in the nuclear localization signal, both predicting a loss of function of the mutated angiogenin, although this remains to be confirmed.
Whether angiogenin is endowed with neurotrophic properties like VEGF, in addition to its angiogenic activity, is not yet established.
See also
ALS genes
| SOD1 | ALS2 | SETX | VAPB | ANG | DCTN1 | MAPT |
References
Lambrechts D, Lafuste P, Carmeliet P, Conway EM. Another angiogenic gene linked to amyotrophic lateral sclerosis. Trends Mol Med. 2006 Aug;12(8):345-7. PMID: #16843725#