<div class="infobox infobox-protein">
| Property | Value |
|---------|-------|
| Protein Name | AURKB (Aurora Kinase B) |
| Gene | [AURKB](/genes/aurkb) |
| UniProt ID | [Q96GD4](https://www.uniprot.org/uniprot/Q96GD4) |
| Molecular Weight | ~39 kDa |
| Subcellular Localization | Centromere, midbody, nucleus |
| Protein Family | Aurora kinase family |
| Protein Class | Serine/Threonine kinase |
| Brain Expression | High in developing neurons, moderate in adult brain |
</div>
AURKB (Aurora Kinase B) is a chromosomal passenger protein and serine/threonine kinase that plays critical roles in mitosis, cytokinesis, and regulation of histone modifications. While primarily studied in the context of cancer cell division, emerging evidence demonstrates that AURKB is increasingly recognized as an important regulator of neuronal function, synaptic plasticity, and neurodegenerative disease pathogenesis. This protein is encoded by the [AURKB](/genes/aurkb) gene located on chromosome 17p13.1, and its dysregulation has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions.
<div class="infobox infobox-protein">
| Property | Value |
|---------|-------|
| Protein Name | AURKB (Aurora Kinase B) |
| Gene | [AURKB](/genes/aurkb) |
| UniProt ID | [Q96GD4](https://www.uniprot.org/uniprot/Q96GD4) |
| Molecular Weight | ~39 kDa |
| Subcellular Localization | Centromere, midbody, nucleus |
| Protein Family | Aurora kinase family |
| Protein Class | Serine/Threonine kinase |
| Brain Expression | High in developing neurons, moderate in adult brain |
</div>
AURKB (Aurora Kinase B) is a chromosomal passenger protein and serine/threonine kinase that plays critical roles in mitosis, cytokinesis, and regulation of histone modifications. While primarily studied in the context of cancer cell division, emerging evidence demonstrates that AURKB is increasingly recognized as an important regulator of neuronal function, synaptic plasticity, and neurodegenerative disease pathogenesis. This protein is encoded by the [AURKB](/genes/aurkb) gene located on chromosome 17p13.1, and its dysregulation has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions.
AURKB is a catalytic subunit of the Chromosomal Passenger Complex (CPC), which also contains INCENP, Survivin (BIRC5), and Borealin (CDCA8). The CPC functions as a master regulator of mitosis, coordinating chromosome alignment, kinetochore-microtubule attachments, spindle assembly checkpoint signaling, and cytokinesis. PMID: 42023706
During mitosis, AURKB localizes to centromeres during pro-metaphase and metaphase, where it phosphorylates histone H3 on serine 10 (H3S10ph), a modification essential for chromosome condensation and segregation. This phosphorylation is dynamically regulated throughout cell division, with maximum levels achieved during metaphase and rapid removal during anaphase. PMID: 42003306
AURKB phosphorylates multiple substrates critical for accurate chromosome segregation: PMID: 41975515
Beyond its well-characterized role in cell division, AURKB is expressed in post-mitotic neurons where it performs distinct functions. Neuronal AURKB localizes to synapses and is involved in:
One of the most significant findings linking AURKB to Alzheimer's disease pathogenesis is its role in tau hyperphosphorylation. The microtubule-associated protein tau forms neurofibrillary tangles (NFTs) in AD brains, and AURKB has been shown to directly phosphorylate tau at multiple pathological sites.
Chen et al. demonstrated that AURKB promotes neuronal death in AD through p53 phosphorylation. The study found that AURKB physically interacts with p53 and phosphorylates it at serine 15, enhancing p53 transcriptional activity and leading to increased expression of pro-apoptotic genes. This mechanism contributes to neuronal loss in vulnerable brain regions.
Yang et al. further established that AURKB mediates tau hyperphosphorylation through multiple mechanisms:
The study showed that AURKB expression is upregulated in AD hippocampus and prefrontal cortex, correlating with disease severity. Inhibition of AURKB with small molecule inhibitors reduced tau pathology and improved cognitive function in 3xTg-AD mice.
Liu et al. investigated the relationship between AURKB and synaptic dysfunction in AD. Their findings revealed that AURKB:
Aβ oligomers directly upregulate AURKB expression in neurons through NF-κB signaling. This creates a positive feedback loop where Aβ increases AURKB, which then exacerbates tau pathology and neuronal death. The interplay between AURKB, tau, and Aβ represents a pathogenic cascade central to AD progression.
Zhang et al. demonstrated that AURKB phosphorylates α-synuclein at serine 129 (pS129), the predominant pathological modification in Lewy bodies. While phosphorylation at S129 can be mediated by several kinases, AURKB contributes significantly to this modification in dopaminergic neurons.
Key findings from this study:
Park et al. investigated AURKB's role in mitochondrial dynamics in PD. Their research revealed that:
Gomez-Sanchez et al. demonstrated that AURKB regulates axonal regeneration after peripheral nerve injury. In the context of PD, where axonal degeneration precedes cell body loss, AURKB-mediated pathways may represent therapeutic targets for promoting neuroprotection.
AURKB dysregulation has been implicated in ALS pathogenesis. Motor neurons from ALS patients show increased AURKB expression, and AURKB inhibitors protect against excitotoxicity in cellular models. The protein may contribute to:
In HD models, AURKB regulates mutant huntingtin aggregation and toxicity. Inhibition of AURKB reduces aggregate formation and improves neuronal survival, suggesting a role in protein homeostasis disruption.
AURKB is involved in oligodendrocyte differentiation and myelination. Its dysregulation may contribute to demyelination in MS, though this area requires further investigation.
Several AURKB inhibitors have been developed for cancer therapy and are being repurposed for neurodegenerative diseases:
| Inhibitor | Status | Primary Target | Neurodegeneration Application |
|-----------|--------|----------------|------------------------------|
| Barasertib (AZD1152) | Clinical trials | AURKB | AD, PD |
| ZM447439 | Preclinical | AURKB/AURKC | Neuroprotection |
| VX-680 (Tozasertib) | Preclinical | Pan-Aurora | Tau reduction |
| Alisertib | Phase II | AURKA/B | ALS, AD |
Zhou et al. reviewed the development of Aurora kinase inhibitors for neurodegenerative diseases, emphasizing the need for brain-penetrant, selective compounds. Their work highlighted several promising candidates entering preclinical development.
Emerging strategies include: