Involvement of Endolysosomes and Aurora Kinase A in the Regulation of Amyloid β Protein Levels in Neurons
Abstract
:1. Introduction
2. Results
2.1. AURKA Is Expressed in Neurons: AURKA Was Highly Present in Primary Cultured Rat Cortical Neurons (Figure 1A)
2.2. Phosphorylated AURKA Is Reduced in Human AD Brain
2.3. AURKA Affects Endolysosome pH
2.4. AURKA Affects Aβ Generation
2.5. AURKA Activity Effects on BACE-1 and Cathepsin D
3. Discussion
4. Materials and Methods
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- DeTure, M.A.; Dickson, D.W. The neuropathological diagnosis of Alzheimer’s disease. Mol. Neurodegener. 2019, 14, 32. [Google Scholar] [CrossRef] [PubMed]
- Van Acker, Z.P.; Bretou, M.; Annaert, W. Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: Impact of genetic risk factors. Mol. Neurodegener. 2019, 14, 20. [Google Scholar] [CrossRef] [PubMed]
- Cataldo, A.M.; Peterhoff, C.M.; Troncoso, J.C.; Gomez-Isla, T.; Hyman, B.T.; Nixon, R.A. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and Down syndrome: Differential effects of APOE genotype and presenilin mutations. Am. J. Pathol. 2000, 157, 277–286. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.; Miller, M.R.; Fernandez, M.A.; Berg, E.L.; Prada, A.M.; Ouyang, Q.; Schmidt, M.; Silverman, J.L.; Young-Pearse, T.L.; Morrow, E.M. Early lysosome defects precede neurodegeneration with amyloid-beta and tau aggregation in NHE6-null rat brain. Brain 2022, 145, 3187–3202. [Google Scholar] [CrossRef] [PubMed]
- McGuire, C.; Stransky, L.; Cotter, K.; Forgac, M. Regulation of V-ATPase activity. Front. Biosci. (Landmark Ed.) 2017, 22, 609–622. [Google Scholar] [PubMed]
- Mindell, J.A. Lysosomal acidification mechanisms. Annu. Rev. Physiol. 2012, 74, 69–86. [Google Scholar] [CrossRef] [PubMed]
- Quintero-Monzon, O.; Martin, M.M.; Fernandez, M.A.; Cappello, C.A.; Krzysiak, A.J.; Osenkowski, P.; Wolfe, M.S. Dissociation between the processivity and total activity of gamma-secretase: Implications for the mechanism of Alzheimer’s disease-causing presenilin mutations. Biochemistry 2011, 50, 9023–9035. [Google Scholar] [CrossRef] [PubMed]
- Sinha, S.; Anderson, J.P.; Barbour, R.; Basi, G.S.; Caccavello, R.; Davis, D.; Doan, M.; Dovey, H.F.; Frigon, N.; Hong, J.; et al. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature 1999, 402, 537–540. [Google Scholar] [CrossRef]
- Suire, C.N.; Abdul-Hay, S.O.; Sahara, T.; Kang, D.; Brizuela, M.K.; Saftig, P.; Dickson, D.W.; Rosenberry, T.L.; Leissring, M.A. Cathepsin D regulates cerebral Abeta42/40 ratios via differential degradation of Abeta42 and Abeta40. Alzheimers Res. Ther. 2020, 12, 80. [Google Scholar] [CrossRef]
- Hook, V.; Toneff, T.; Bogyo, M.; Greenbaum, D.; Medzihradszky, K.F.; Neveu, J.; Lane, W.; Hook, G.; Reisine, T. Inhibition of cathepsin B reduces beta-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: Evidence for cathepsin B as a candidate beta-secretase of Alzheimer’s disease. Biol. Chem. 2005, 386, 931–940. [Google Scholar] [CrossRef]
- Lee, J.H.; Yang, D.S.; Goulbourne, C.N.; Im, E.; Stavrides, P.; Pensalfini, A.; Chan, H.; Bouchet-Marquis, C.; Bleiwas, C.; Berg, M.J.; et al. Faulty autolysosome acidification in Alzheimer’s disease mouse models induces autophagic build-up of Abeta in neurons, yielding senile plaques. Nat. Neurosci. 2022, 25, 688–701. [Google Scholar] [CrossRef] [PubMed]
- Hui, L.; Chen, X.; Geiger, J.D. Endolysosome involvement in LDL cholesterol-induced Alzheimer’s disease-like pathology in primary cultured neurons. Life Sci. 2012, 91, 1159–1168. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Hui, L.; Geiger, N.H.; Haughey, N.J.; Geiger, J.D. Endolysosome involvement in HIV-1 transactivator protein-induced neuronal amyloid beta production. Neurobiol. Aging 2013, 34, 2370–2378. [Google Scholar] [CrossRef] [PubMed]
- Hui, L.; Soliman, M.L.; Geiger, N.H.; Miller, N.M.; Afghah, Z.; Lakpa, K.L.; Chen, X.; Geiger, J.D. Acidifying Endolysosomes Prevented Low-Density Lipoprotein-Induced Amyloidogenesis. J. Alzheimer’s Dis. 2019, 67, 393–410. [Google Scholar] [CrossRef] [PubMed]
- Hui, L.; Ye, Y.; Soliman, M.L.; Lakpa, K.L.; Miller, N.M.; Afghah, Z.; Geiger, J.D.; Chen, X. Antiretroviral Drugs Promote Amyloidogenesis by De-Acidifying Endolysosomes. J. Neuroimmune Pharmacol. 2021, 16, 159–168. [Google Scholar] [CrossRef] [PubMed]
- Nikonova, A.S.; Astsaturov, I.; Serebriiskii, I.G.; Dunbrack, R.L., Jr.; Golemis, E.A. Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol. Life Sci. 2013, 70, 661–687. [Google Scholar] [CrossRef] [PubMed]
- Takitoh, T.; Kumamoto, K.; Wang, C.-C.; Sato, M.; Toba, S.; Wynshaw-Boris, A.; Hirotsune, S. Activation of Aurora-A is essential for neuronal migration via modulation of microtubule organization. J. Neurosci. 2012, 32, 11050–11066. [Google Scholar] [CrossRef] [PubMed]
- Blazejewski, S.M.; Bennison, S.A.; Liu, X.; Toyo-Oka, K. High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching. Sci. Rep. 2021, 11, 8156. [Google Scholar] [CrossRef] [PubMed]
- Mori, D.; Yamada, M.; Mimori-Kiyosue, Y.; Shirai, Y.; Suzuki, A.; Ohno, S.; Saya, H.; Wynshaw-Boris, A.; Hirotsune, S. An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite elongation by modulation of microtubule dynamics. Nat. Cell Biol. 2009, 11, 1057–1068. [Google Scholar] [CrossRef]
- Rosenberger, A.F.; Hilhorst, R.; Coart, E.; García Barrado, L.; Naji, F.; Rozemuller, A.J.; van der Flier, W.M.; Scheltens, P.; Hoozemans, J.J.; van der Vies, S.M. Protein kinase activity decreases with higher Braak stages of Alzheimer’s disease pathology. J. Alzheimer’s Dis. 2016, 49, 927–943. [Google Scholar] [CrossRef]
- Al-bataineh, M.M.; Alzamora, R.; Ohmi, K.; Ho, P.-Y.; Marciszyn, A.L.; Gong, F.; Li, H.; Hallows, K.R.; Pastor-Soler, N.M. Aurora kinase A activates the vacuolar H+-ATPase (V-ATPase) in kidney carcinoma cells. Am. J. Physiol.-Ren. Physiol. 2016, 310, F1216–F1228. [Google Scholar] [CrossRef] [PubMed]
- Stockley, J.; O’Neill, C. Understanding BACE1: Essential protease for amyloid-β production in Alzheimer’s disease. Cell. Mol. Life Sci. 2008, 65, 3265–3289. [Google Scholar] [CrossRef] [PubMed]
- Hamazaki, H. Cathepsin D is involved in the clearance of Alzheimer’s beta-amyloid protein. FEBS Lett. 1996, 396, 139–142. [Google Scholar] [CrossRef]
- Cunningham, M.; Tang, J. Purification and properties of cathepsin D from porcine spleen. J. Biol. Chem. 1976, 251, 4528–4536. [Google Scholar] [CrossRef]
- Gieselmann, V.; Hasilik, A.; von Figura, K. Processing of human cathepsin D in lysosomes in vitro. J. Biol. Chem. 1985, 260, 3215–3220. [Google Scholar] [CrossRef] [PubMed]
- Minarowska, A.; Karwowska, A.; Gacko, M. Quantitative determination and localization of cathepsin D and its inhibitors. Folia Histochem. Cytobiol. 2009, 47, 153–177. [Google Scholar] [CrossRef] [PubMed]
- Avrahami, L.; Farfara, D.; Shaham-Kol, M.; Vassar, R.; Frenkel, D.; Eldar-Finkelman, H. Inhibition of Glycogen Synthase Kinase-3 Ameliorates β-Amyloid Pathology and Restores Lysosomal Acidification and Mammalian Target of Rapamycin Activity in the Alzheimer Disease Mouse Model In Vivo and In Vitro Studies. J. Biol. Chem. 2013, 288, 1295–1306. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.S.; Chen, W.N.; Zhou, M.; Arttamangkul, S.; Haugland, R.P. Probing the cathepsin D using a BODIPY FL-pepstatin A: Applications in fluorescence polarization and microscopy. J. Biochem. Biophys. Methods 2000, 42, 137–151. [Google Scholar] [CrossRef]
- Rodriguez-Rios, M.; McHugh, B.J.; Liang, Z.; Megia-Fernandez, A.; Lilienkampf, A.; Dockrell, D.; Bradley, M. A fluorogenic, peptide-based probe for the detection of Cathepsin D in macrophages. Commun. Chem. 2023, 6, 237. [Google Scholar] [CrossRef]
- Wang, S.; Qi, J.; Zhu, M.; Wang, M.; Nie, J. AURKA rs2273535 T> A Polymorphism Associated With Cancer Risk: A Systematic Review With Meta-Analysis. Front. Oncol. 2020, 10, 1040. [Google Scholar] [CrossRef]
- Humme, D.; Haider, A.; Möbs, M.; Mitsui, H.; Suárez-Fariñas, M.; Ohmatsu, H.; Geilen, C.I.; Eberle, J.; Krueger, J.G.; Beyer, M. Aurora kinase A is upregulated in cutaneous T-cell lymphoma and represents a potential therapeutic target. J. Investig. Dermatol. 2015, 135, 2292–2300. [Google Scholar] [CrossRef] [PubMed]
- Bertolin, G.; Bulteau, A.L.; Alves-Guerra, M.C.; Burel, A.; Lavault, M.T.; Gavard, O.; Le Bras, S.; Gagne, J.P.; Poirier, G.G.; Le Borgne, R.; et al. Aurora kinase A localises to mitochondria to control organelle dynamics and energy production. Elife 2018, 7, e38111. [Google Scholar] [CrossRef]
- Bertolin, G.; Alves-Guerra, M.C.; Cheron, A.; Burel, A.; Prigent, C.; Le Borgne, R.; Tramier, M. Mitochondrial Aurora kinase A induces mitophagy by interacting with MAP1LC3 and Prohibitin 2. Life Sci. Alliance 2021, 4, e202000806. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, T.T.T.; Shang, E.; Shu, C.; Kim, S.; Mela, A.; Humala, N.; Mahajan, A.; Yang, H.W.; Akman, H.O.; Quinzii, C.M.; et al. Aurora kinase A inhibition reverses the Warburg effect and elicits unique metabolic vulnerabilities in glioblastoma. Nat. Commun. 2021, 12, 5203. [Google Scholar] [CrossRef]
- Gyure, K.A.; Durham, R.; Stewart, W.F.; Smialek, J.E.; Troncoso, J.C. Intraneuronal Aβ-amyloid precedes development of amyloid plaques in Down syndrome. Arch. Pathol. Lab. Med. 2001, 125, 489–492. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Afghah, Z.; Khan, N.; Datta, G.; Halcrow, P.W.; Geiger, J.D.; Chen, X. Involvement of Endolysosomes and Aurora Kinase A in the Regulation of Amyloid β Protein Levels in Neurons. Int. J. Mol. Sci. 2024, 25, 6200. https://doi.org/10.3390/ijms25116200
Afghah Z, Khan N, Datta G, Halcrow PW, Geiger JD, Chen X. Involvement of Endolysosomes and Aurora Kinase A in the Regulation of Amyloid β Protein Levels in Neurons. International Journal of Molecular Sciences. 2024; 25(11):6200. https://doi.org/10.3390/ijms25116200
Chicago/Turabian StyleAfghah, Zahra, Nabab Khan, Gaurav Datta, Peter W. Halcrow, Jonathan D. Geiger, and Xuesong Chen. 2024. "Involvement of Endolysosomes and Aurora Kinase A in the Regulation of Amyloid β Protein Levels in Neurons" International Journal of Molecular Sciences 25, no. 11: 6200. https://doi.org/10.3390/ijms25116200