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- Title
Involvement of Endolysosomes and Aurora Kinase A in the Regulation of Amyloid β Protein Levels in Neurons.
- Authors
Afghah, Zahra; Khan, Nabab; Datta, Gaurav; Halcrow, Peter W.; Geiger, Jonathan D.; Chen, Xuesong
- 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.
- Subjects
AURORA kinases; CATHEPSIN D; AMYLOID; NEURONS; AMYLOID plaque; TUBULINS; AMYLOID beta-protein precursor
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 11, p6200
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25116200