AURKA (Aurora Kinase A) encodes a serine/threonine kinase essential for mitotic entry, centrosome maturation, and spindle assembly[1]. While primarily studied in cancer biology due to its frequent overexpression in tumors, AURKA also has important functions in post-mitotic neurons, including roles in cilia function, neuronal polarity, and dendrite morphogenesis[2]. Dysregulated AURKA may contribute to neurodegeneration through effects on cell cycle re-entry in neurons, a hallmark of several neurodegenerative diseases[3].
| Property | Value |
|---|---|
| Gene Symbol | AURKA |
| Full Name | Aurora Kinase A |
| Chromosomal Location | 20q13.2 |
| NCBI Gene ID | 6790 |
| OMIM | 603072 |
| Ensembl ID | ENSG00000087586 |
| UniProt ID | O14965 |
| Alias | AURA, BTAK, STK15, STK6 |
AURKA is a member of the Aurora family of serine/threonine kinases, which also includes AURKB (Aurora Kinase B) and AURKC (Aurora Kinase C)[4]. The protein has a conserved kinase domain flanked by N-terminal regulatory regions and C-terminal degradation motifs.
AURKA kinase activity is tightly regulated:
AURKA shows high expression in proliferating cells, but is also expressed in certain post-mitotic tissues:
In the nervous system, AURKA is expressed in:
The expression in mature neurons is typically low but can be upregulated under certain conditions, including cellular stress and disease states[5].
AURKA's canonical functions in dividing cells include[6]:
In neurons, AURKA has additional specialized roles[7]:
One of the leading theories in neurodegeneration is that neurons inappropriately re-enter the cell cycle, leading to apoptotic cell death[8]. AURKA plays a central role in this process:
AURKA has been specifically implicated in Alzheimer's disease[9]:
In Parkinson's disease models[10]:
ALS research suggests[11]:
AURKA is a validated cancer target, with several inhibitors in clinical development[12]:
| Drug | Company | Stage | Notes |
|---|---|---|---|
| Alisertib (MLN8237) | Millennium/Takeda | Phase III | Oral selective inhibitor |
| VX-680 (Tozasertib) | Vertex | Discontinued | First-generation inhibitor |
| Danusertib | Novartis | Phase II | Pan-Aurora inhibitor |
AURKA modulation for neurodegeneration is speculative but intriguing:
| Variant | Effect | Associated Cancer |
|---|---|---|
| F31I | Gain of function | Breast cancer |
| V57I | Moderate activity | Various |
| L210F | Amplification | Ovarian cancer |
While no direct disease-causing mutations are known, expression quantitative trait loci (eQTLs) may modify disease risk.
AURKA is a serine/threonine kinase with essential functions in cell division and emerging roles in neuronal biology. While best known as a cancer target, AURKA dysregulation may contribute to neurodegenerative diseases through aberrant cell cycle re-entry in neurons. Further research is needed to determine whether AURKA modulation could have therapeutic benefits in neurodegeneration.
Giet et al. The Aurora kinase family in cell division. Nature Reviews Cancer. 2010. ↩︎
Barr & Gergely. Aurora-A: the maker and breaker of spindle poles. Journal of Cell Science. 2007. ↩︎
Zhu et al. Cell cycle re-entry in neurodegeneration. Molecular Brain. 2014. ↩︎
Carmena & Earnshaw. The cellular geography of the aurora kinases. Nature Reviews Molecular Cell Biology. 2003. ↩︎
Sardon et al. Aurora-A in adult neurons. Cell Cycle. 2010. ↩︎
Marumoto et al. Aurora-A - a mitotic serine-threonine kinase. Journal of Biochemistry. 2003. ↩︎
Leroux et al. Aurora-A and cilia. Developmental Cell. 2017. ↩︎
Herrup & Yang. Cell cycle regulation in post-mitotic neurons. Cell Cycle. 2007. ↩︎
Zhu et al. Aurora kinase A in Alzheimer's disease. Molecular Brain. 2014. ↩︎
Liu et al. Aurora-A and Parkinson's disease. Journal of Parkinson's Disease. 2015. ↩︎
Ranganathan et al. Cell cycle activation in ALS. Experimental Neurology. 2009. ↩︎
Cheung et al. Clinical development of Aurora kinase inhibitors. Current Topics in Medicinal Chemistry. 2011. ↩︎