| ANG — Angiogenin | |
|---|---|
| Symbol | ANG |
| Full Name | Angiogenin |
| Chromosome | 14q11.2 |
| NCBI Gene | 283 |
| Ensembl | ENSG00000214402 |
| OMIM | 105850 |
| UniProt | P03950 |
| Protein Name | Angiogenin |
| Protein Length | 147 amino acids |
| Molecular Weight | 16.5 kDa |
| Brain Expression | High: motor cortex, spinal cord, brainstem, hippocampus |
| Subcellular Localization | Cytoplasm, Nucleus, Extracellular (secreted) |
| Associated Diseases | Amyotrophic Lateral Sclerosis, Parkinson's Disease |
Ang Gene Angiogenin plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
ANG (Angiogenin) is a member of the secreted RNase family that plays important roles in both angiogenesis and cellular stress response[1]. Originally characterized for its angiogenic activity, angiogenin has emerged as a critical factor in neurodegenerative disease, particularly amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD)[2].
Angiogenin is a 147-amino acid secreted protein that belongs to the pancreatic ribonuclease family. Unlike other family members, angiogenin has acquired specialized functions in neuronal survival, stress granule dynamics, and innate immunity[1:1]. Mutations in ANG are associated with both familial and sporadic ALS, making it an important gene in understanding motor neuron disease pathogenesis[2:1].
The ANG gene is located on chromosome 14q11.2 and consists of 3 exons[1:2]. The gene encodes a secreted protein with a classic signal peptide for extracellular secretion.
Angiogenin has a characteristic RNase fold with several key structural features[3]:
| Residue | Function |
|---|---|
| His13 | Catalytic histidine |
| Lys41 | Substrate binding |
| Arg31 | RNA binding |
| Cys39 | Disulfide bond formation |
Angiogenin retains ribonuclease activity, though weaker than RNase A[1:3]:
Upon cellular stress, angiogenin translocates to the nucleus[4]:
Angiogenin localizes to stress granules under cellular stress[5]:
Angiogenin provides neuroprotection through multiple mechanisms[6]:
ANG is expressed in regions vulnerable to neurodegeneration[2:2]:
Angiogenin is expressed in:
ANG mutations were first linked to ALS in 2006 by Wu et al.[2:3]:
Disease-causing Mutations:
| Mutation | Effect | Phenotype |
|---|---|---|
| K17I | Reduced angiogenic activity | ALS |
| R31L | Impaired nuclear translocation | ALS/PD |
| C39G | Loss of secretion | ALS |
| P110L | Altered RNase activity | ALS |
| Q12L | Reduced stress response | ALS |
Mechanism:
ANG is implicated in PD through[8]:
Angiogenin dysregulation is observed in:
Angiogenin promotes blood vessel formation through[3:1]:
Under cellular stress, angiogenin mediates protective responses[4:1][5:1]:
Angiogenin interacts with:
Angiogenin is being developed as a neuroprotective therapeutic[9]:
AAV-mediated ANG delivery:
Pharmacological approaches include:
Ang Gene Angiogenin plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
The study of Ang Gene Angiogenin has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Subramanian V, Crabtree B, Badii M, et al. Angiogenin as a molecular target for ALS and its potential as a multi-target therapeutic strategy. Free Radic Biol Med. 2018;120: S45. PubMed
Gao X, Xu H, Zhang L, et al. Angiogenin protects motor neurons from apoptosis induced by oxidative stress. Cell Mol Neurobiol. 2017;37(5): 805-815. PubMed
Kieran D, Sebastia J, Greenway MJ, et al. Control of mitochondrial function and neuroprotection by angiogenin. EMBO J. 2008;27(20): 2553-2565. PubMed
Li S, Zhang L, Zhou Q, et al. Angiogenin deficiency leads to mitochondrial dysfunction in a PINK1/Parkin-dependent manner. J Mol Neurosci. 2020;70(10): 1642-1655. PubMed
Steidinger TU, Standaert DG, Yacoubian TA. Angiogenin and neuroinflammation: new insights into ALS and Parkinson's disease. Neurobiol Dis. 2019;130: 104478. PubMed
Campesi I, Occhioni S, Montella A, et al. Angiogenin and inflammatory markers in neurodegenerative diseases. J Neurol Sci. 2016;370: 258-264. PubMed
Thiyagaragan M, Tiwari R, Arora R, et al. Angiogenin-mediated rRNA transcription and ribosome biogenesis in neuroprotection. Mol Neurobiol. 2021;58(9): 4678-4691. PubMed
Wu D, Yu W, Kishikawa H, et al. Angiogenin loss-of-function mutations in familial amyotrophic lateral sclerosis. Nat Genet. 2007;39(8): 969-972. PubMed
Wu D, et al. (2006). Angiogenin mutations in ALS. Science, 313(5794), 1818-1821. ↩︎ ↩︎ ↩︎ ↩︎
Shapiro R, et al. (2007). Structure of angiogenin. Acta Crystallogr D Biol Crystallogr, 63(Pt 1), 162-168. ↩︎ ↩︎
Tsuji T, et al. (2005). Nuclear translocation of angiogenin. Mol Cell Biol, 25(1), 97-112. ↩︎ ↩︎
Emara S, et al. (2012). Angiogenin and stress granules. J Biol Chem, 287(11), 8106-8114. ↩︎ ↩︎
Subramanian V, et al. (2008). Neuroprotective functions of angiogenin. Mol Neurobiol, 38(3), 185-199. ↩︎
Stecn K, et al. (2010). ANG mutations and ALS pathogenesis. Neurology, 75(1), 44-50. ↩︎
van Es MA, et al. (2011). Angiogenin variants in PD. Lancet Neurol, 10(9), 808-818. ↩︎
Kieran D, et al. (2008). Therapeutic potential of angiogenin. Proc Natl Acad Sci USA, 105(2), 679-684. ↩︎