# Involvement of Endolysosomes and Aurora Kinase A in the Regulation of Amyloid β Protein Levels in Neurons

## TL;DR

This study shows that Aurora kinase A helps regulate amyloid beta levels in neurons, and its reduced activity in Alzheimer's disease may contribute to amyloid plaque formation.

## Contribution

The study reveals a novel role of Aurora kinase A in modulating amyloid beta levels via endolysosomal regulation in neurons.

## Key findings

- AURKA phosphorylation is reduced in human Alzheimer's disease brains.
- AURKA activation acidifies endolysosomes and reduces Aβ levels by modulating BACE-1 and cathepsin D.
- AURKA inhibition increases Aβ levels by de-acidifying endolysosomes and reducing cathepsin D activity.

## Abstract

Aurora kinase A (AURKA) is a serine/threonine-protein kinase that regulates microtubule organization during neuron migration and neurite formation. Decreased activity of AURKA was found in Alzheimer’s disease (AD) brain samples, but little is known about the role of AURKA in AD pathogenesis. Here, we demonstrate that AURKA is expressed in primary cultured rat neurons, neurons from adult mouse brains, and neurons in postmortem human AD brains. AURKA phosphorylation, which positively correlates with its activity, is reduced in human AD brains. In SH-SY5Y cells, pharmacological activation of AURKA increased AURKA phosphorylation, acidified endolysosomes, decreased the activity of amyloid beta protein (Aβ) generating enzyme β-site amyloid precursor protein cleaving enzyme (BACE-1), increased the activity of the Aβ degrading enzyme cathepsin D, and decreased the intracellular and secreted levels of Aβ. Conversely, pharmacological inhibition of AURKA decreased AURKA phosphorylation, de-acidified endolysosomes, decreased the activity of cathepsin D, and increased intracellular and secreted levels of Aβ. Thus, reduced AURKA activity in AD may contribute to the development of intraneuronal accumulations of Aβ and extracellular amyloid plaque formation.