Genetic Modulators of Prion-Like Protein Propagation in Alzheimer's Disease

Authors

  • Alaina Shinde Edison High School

DOI:

https://doi.org/10.47611/jsrhs.v13i2.6734

Keywords:

Protein Propagation, Alzheimer’s Disease, Prions, Tau, Beta-amyloid, Cellular Prion Protein

Abstract

Alzheimer's disease (AD) is a widespread neurodegenerative disorder with complex causes. Starting with a historical overview, this paper traces the foundational discoveries by Alois Alzheimer and subsequent research into the roles of Tau, beta-amyloid (Aß), and cellular prion protein (PrPc) in AD progression. The familial aspect of AD is discussed, highlighting genetic mutations in key genes such as APP, PSEN1, PSEN2, MAPT, and APOE. Additionally, it explores epigenetic factors in familial AD and examines the prion-like behavior of Tau and Aß proteins. Potential therapeutic targets arising from these insights are considered, including PRNP manipulation and modulation of Tau and Aß behavior. A proposed stem cell therapy aims to target and counteract the pathological activities of Tau and Aß proteins through strategic genetic modifications, precise delivery to affected brain regions, and controlled release systems for sustained therapeutic effects. Ethical considerations and limitations in AD research are also addressed, emphasizing the importance of responsible research practices and equitable access to treatments. Through this exploration, the text underscores the ongoing efforts to unravel the complexities of AD and develop effective strategies for its management. 

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References or Bibliography

Ashe, K. H., & Aguzzi, A. (2013). Prions, prionoids and pathogenic proteins in Alzheimer disease. Prion, 7(1), 55–59. https://doi.org/10.4161/pri.23061

Ayanoglu, F. B., Elcin, A. E., & Elcin, Y. M. (2020). Bioethical Issues in Genome Editing by the CRISPR/Cas9 Technology. Turkish Journal of Biology, 44(2). https://doi.org/10.3906/biy-1912-52

Berdyński, M., Miszta, P., Safranow, K., Andersen, P. M., Morita, M., Filipek, S., Żekanowski, C., & Kuźma-Kozakiewicz, M. (2022). SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity. Scientific Reports, 12(1), 103. https://doi.org/10.1038/s41598-021-03891-8

D’Argenio, V., & Sarnataro, D. (2020). New Insights into the Molecular Bases of Familial Alzheimer’s Disease. Journal of Personalized Medicine, 10(2). https://doi.org/10.3390/jpm10020026

Fluharty, B. R., Biasini, E., Stravalaci, M., Sclip, A., Diomede, L., Balducci, C., Vitola, P. L., Messa, M., Colombo, L., Forloni, G., Borsello, T., Gobbi, M., & Harris, D. A. (2013). An N-terminal Fragment of the Prion Protein Binds to Amyloid-β Oligomers and Inhibits Their Neurotoxicity in Vivo*. Journal of Biological Chemistry, 288(11), 7857–7866. https://doi.org/10.1074/jbc.M112.423954

Hyun, I., Scharf-Deering, J. C., & Lunshof, J. E. (2020). Ethical issues related to brain organoid research. Brain Research, 1732, 146653. https://doi.org/10.1016/j.brainres.2020.146653

Kellett, K. A. B., & Hooper, N. M. (2009). Prion protein and Alzheimer disease. Prion, 3(4), 190–194. https://doi.org/10.4161/pri.3.4.9980

Kent, S. A., Spires-Jones, T. L., & Durrant, C. S. (2020). The physiological roles of tau and Aβ: implications for Alzheimer’s disease pathology and therapeutics. Acta Neuropathologica. https://doi.org/10.1007/s00401-020-02196-w

Lanoiselée, H.-M., Nicolas, G., Wallon, D., Rovelet-Lecrux, A., Lacour, M., Rousseau, S., Richard, A.-C., Pasquier, F., Rollin-Sillaire, A., Martinaud, O., Quillard-Muraine, M., de la Sayette, V., Boutoleau-Bretonniere, C., Etcharry-Bouyx, F., Chauviré, V., Sarazin, M., le Ber, I., Epelbaum, S., Jonveaux, T., & Rouaud, O. (2017). APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Medicine, 14(3). https://doi.org/10.1371/journal.pmed.1002270

Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013). Apolipoprotein E and Alzheimer disease: risk, Mechanisms and Therapy. Nature Reviews Neurology, 9(2), 106–118. https://doi.org/10.1038/nrneurol.2012.263

Liu, H., Farr-Jones, S., Ulyanov, N. B., Llinás, M., Marqusee, S., Groth, D., Cohen, F. E., Prusiner, S. B., & Thomas Leroy James. (1999). Solution Structure of Syrian Hamster Prion Protein rPrP(90−231). 38(17), 5362–5377. https://doi.org/10.1021/bi982878x

Mansour, A., Romani, M., Acharya, A. B., Rahman, B., Verron, E., & Badran, Z. (2023). Drug Delivery Systems in Regenerative Medicine: An Updated Review. Pharmaceutics, 15(2), 695. https://doi.org/10.3390/pharmaceutics15020695

Neundörfer, G. (2003). The discovery of Alzheimer’s disease. Dialogues in Clinical Neuroscience, 5(1), 101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181715/

Nussbaum, J. M., Seward, M. E., & Bloom, G. S. (2013). Alzheimer disease. Prion, 7(1), 14–19. https://doi.org/10.4161/pri.22118

Nygaard, H. B. (2018). Targeting Fyn Kinase in Alzheimer’s Disease. Biological Psychiatry, 83(4), 369–376. https://doi.org/10.1016/j.biopsych.2017.06.004

Perry, R. T., Go, P., Harrell, L. E., & Acton, R. T. (1995). SSCP analysis and sequencing of the human prion protein gene (PRNP) detects two different 24 bp deletions in an atypical Alzheimer’s disease family. American Journal of Medical Genetics, 60(1), 12–18. https://doi.org/10.1002/ajmg.1320600104

Raulin, A.-C., Doss, S. V., Trottier, Z. A., Ikezu, T. C., Bu, G., & Liu, C.-C. (2022). ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies. Molecular Neurodegeneration, 17(1). https://doi.org/10.1186/s13024-022-00574-4

Ritchie, D. L., & Barria, M. A. (2021). Prion Diseases: A Unique Transmissible Agent or a Model for Neurodegenerative Diseases? Biomolecules, 11(2), 207. https://doi.org/10.3390/biom11020207

Sakono, M., & Zako, T. (2010). Amyloid oligomers: formation and toxicity of Aβ oligomers. FEBS Journal, 277(6), 1348–1358. https://doi.org/10.1111/j.1742-4658.2010.07568.x

Santana, D. A., Smith, M. de A. C., & Chen, E. S. (2023). Histone Modifications in Alzheimer’s Disease. Genes, 14(2), 347. https://doi.org/10.3390/genes14020347

Sharma, V. K., Mehta, V., & Singh, T. G. (2020). Alzheimer’s Disorder: Epigenetic connection and associated risk factors. Current Neuropharmacology, 18(8). https://doi.org/10.2174/1570159X18666200128125641

Sivandzade, F., & Cucullo, L. (2021). Regenerative Stem Cell Therapy for Neurodegenerative Diseases: An Overview. International Journal of Molecular Sciences, 22(4), 2153. https://doi.org/10.3390/ijms22042153

Smith, R. G., Hannon, E., De Jager, P. L., Chibnik, L., Lott, S. J., Condliffe, D., Smith, A. R., Haroutunian, V., Troakes, C., Al-Sarraj, S., Bennett, D. A., Powell, J., Lovestone, S., Schalkwyk, L., Mill, J., & Lunnon, K. (2018). Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer’s disease neuropathology. Alzheimer’s & Dementia, 14(12), 1580–1588. https://doi.org/10.1016/j.jalz.2018.01.017

Strang, K. H., Golde, T. E., & Giasson, B. I. (2019). MAPT mutations, tauopathy, and mechanisms of neurodegeneration. Laboratory Investigation, 99(7), 912–928. https://doi.org/10.1038/s41374-019-0197-x

Tanzi, R. E., Kovacs, D. M., Kim, T.-W., Moir, R. D., Guenette, S. Y., & Wasco, W. (1996). REVIEWThe Gene Defects Responsible for Familial Alzheimer’s Disease. Neurobiology of Disease, 3(3), 159–168. https://doi.org/10.1006/nbdi.1996.0016

Xue, G., Chen, C., Lu, Z.-L., & Dong, Q. (2010). Brain Imaging Techniques and Their Applications in Decision-Making Research. Acta Psychologica Sinica, 42(1), 120–137. https://doi.org/10.3724/sp.j.1041.2010.00120

Yagi, T., Ito, D., Okada, Y., Akamatsu, W., Nihei, Y., Yoshizaki, T., Yamanaka, S., Okano, H., & Suzuki, N. (2011). Modeling familial Alzheimer’s disease with induced pluripotent stem cells. Human Molecular Genetics, 20(23), 4530–4539. https://doi.org/10.1093/hmg/ddr394

Younan, N. D., Chen, K.-F., Rose, R.-S., Crowther, D. C., & Viles, J. H. (2018). Prion protein stabilizes amyloid-β (Aβ) oligomers and enhances Aβ neurotoxicity in a Drosophila model of Alzheimer’s disease. Journal of Biological Chemistry, 293(34), 13090–13099. https://doi.org/10.1074/jbc.ra118.003319

Younesian, S., Yousefi, A.-M., Momeny, M., Ghaffari, S. H., & Bashash, D. (2022). The DNA Methylation in Neurological Diseases. Cells, 11(21), 3439. https://doi.org/10.3390/cells11213439

Yu, C.-C., Jiang, T., Yang, A.-F., Du, Y.-J., Wu, M., & Kong, L.-H. (2019). Epigenetic Modulation on Tau Phosphorylation in Alzheimer’s Disease. Neural Plasticity, 2019, 1–12. https://doi.org/10.1155/2019/6856327

Yu, Y., Liu, J., Li, S.-Q., Peng, L., & Ye, R. D. (2013). Serum Amyloid A Differentially Activates Microglia and Astrocytes via the PI3K Pathway. Journal of Alzheimer’s Disease, 38(1), 133–144. https://doi.org/10.3233/jad-130818

World Health Organization. (2023). Dementia. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/dementia

Zhang, N. (2015). Epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals. Animal Nutrition, 1(3), 144–151. https://doi.org/10.1016/j.aninu.2015.09.002

Zhou. (2013). Alzheimer’s Disease and Prion Protein. Intractable & Rare Diseases Research. https://doi.org/10.5582/irdr.2013.v2.2.35

Published

05-31-2024

How to Cite

Shinde, A. (2024). Genetic Modulators of Prion-Like Protein Propagation in Alzheimer’s Disease. Journal of Student Research, 13(2). https://doi.org/10.47611/jsrhs.v13i2.6734

Issue

Section

HS Review Articles