Yeast-Based Therapeutic Platforms for Alzheimer’s Disease

Authors

  • Xingyu Lu

DOI:

https://doi.org/10.54097/ebecyp21

Keywords:

Alzheimer’s Disease; Therapeutic peptides; CRISPR; yeast engineering; AI-assisted protein design.

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that represents a growing global health crisis. Existing treatments provide only limited symptomatic relief and fail to stop or reverse disease progression. Therapeutic peptides and proteins such as Anticalin and neprilysin (NEP) show great potential to target the underlying mechanisms of AD by binding, degrading, or preventing the aggregation of amyloid beta (Aβ) and Tau proteins. Yet, large-scale production of biologics in mammalian cell systems is costly and restricts global accessibility. Yeast-based cell factories, especially Pichia pastoris, provide a promising alternative, combining scalability, cost-effectiveness, and safety. Through synthetic biology, fermentation optimization, and protein stabilization, yeast platforms can produce therapeutic peptides at high yield and low cost. This paper discusses the pathology of AD, the therapeutic potential of peptides, strategies for expression in yeast, and the opportunities and challenges in applying microbial systems to neurodegenerative disease treatment. Future perspectives, including CRISPR-based yeast engineering, AI-assisted protein design, and novel delivery methods, are also discussed. Yeast cell factories thus offer a pathway toward affordable peptide-based treatments for AD, bridging the gap between laboratory research and clinical application.

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References

[1] “2023 Alzheimer's disease facts and figures.” Alzheimer's & dementia: the journal of the Alzheimer's Association vol. 19,4 (2023): 1598-1695. doi:10.1002/alz.13016

[2] Jack, Clifford R Jr et al. “NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease.” Alzheimer's & dementia: the journal of the Alzheimer's Association vol. 14,4 (2018): 535-562. doi: 10.1016/j.jalz.2018.02.018

[3] Lannfelt, L et al. “Amyloid-ß-directed immunotherapy for Alzheimer's disease.” Journal of internal medicinevol. 275,3 (2014): 284-95. doi:10.1111/joim.12168

[4] Arnau, José et al. “Current strategies for the use of affinity tags and tag removal for the purification of recombinant proteins.” Protein expression and purification vol. 48,1 (2006): 1-13. doi: 10.1016/j.pep.2005.12.002

[5] Gasser, Brigitte et al. “Protein folding and conformational stress in microbial cells producing recombinant proteins: a host comparative overview.” Microbial cell factories vol. 7 11. 4 Apr. 2008, doi:10.1186/1475-2859-7-11

[6] Walsh, Gary, and Eithne Walsh. “Biopharmaceutical benchmarks 2022.” Nature biotechnology vol. 40,12 (2022): 1722-1760. doi:10.1038/s41587-022-01582-x

[7] Heneka, Michael T et al. “Neuroinflammation in Alzheimer disease.” Nature reviews. Immunology vol. 25,5 (2025): 321-352. doi:10.1038/s41577-024-01104-7

[8] Koch, Giacomo, and Danny Spampinato. “Alzheimer disease and neuroplasticity.” Handbook of clinical neurology vol. 184 (2022): 473-479. doi:10.1016/B978-0-12-819410-2.00027-8

[9] Eskandari, Azadeh et al. “Current achievements, strategies, obstacles, and overcoming the challenges of the protein engineering in Pichia pastoris expression system.” World journal of microbiology & biotechnology vol. 40,1 39. 8 Dec. 2023, doi:10.1007/s11274-023-03851-6

[10] Gagné, Donald et al. “Strategies for the production of isotopically labelled Fab fragments of therapeutic antibodies in Komagataella phaffii (Pichia pastoris) and Escherichia coli for NMR studies.” PloS one vol. 18,11 e0294406. 29 Nov. 2023, doi: 10.1371/journal.pone.0294406

[11] Veronese, F M. “Peptide and protein PEGylation: a review of problems and solutions.” Biomaterials vol. 22,5 (2001): 405-17. doi:10.1016/s0142-9612(00)00193-9

[12] Aisen, Paul S et al. “On the path to 2025: understanding the Alzheimer's disease continuum.” Alzheimer's research & therapy vol. 9,1 60. 9 Aug. 2017, doi:10.1186/s13195-017-0283-5

[13] Hamilton, Stephen R et al. “Humanization of yeast to produce complex terminally sialylated glycoproteins.” Science (New York, N.Y.) vol. 313,5792 (2006): 1441-3. doi:10.1126/science.1130256

[14] Potgieter, Thomas I et al. “Production of monoclonal antibodies by glycoengineered Pichia pastoris.” Journal of biotechnology vol. 139,4 (2009): 318-25. doi: 10.1016/j.jbiotec.2008.12.015

[15] Weidner, Maria et al. “Expression of recombinant proteins in the methylotrophic yeast Pichia pastoris.” Journal of visualized experiments: JoVE ,36 1862. 25 Feb. 2010, doi:10.3791/1862

[16] Gelsinger, Diego Rivera et al. “Bacterial genome engineering using CRISPR-associated transposases.” Nature protocols vol. 19,3 (2024): 752-790. doi:10.1038/s41596-023-00927-3

[17] Spriestersbach, Anne et al. “Purification of His-Tagged Proteins.” Methods in enzymology vol. 559 (2015): 1-15. doi: 10.1016/bs.mie.2014.11.003

[18] Ahmad, Mudassar et al. “Protein expression in Pichia pastoris: recent achievements and perspectives for heterologous protein production.” Applied microbiology and biotechnology vol. 98,12 (2014): 5301-17. doi:10.1007/s00253-014-5732-5

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Published

28-12-2025

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Section

Articles

How to Cite

Lu, X. (2025). Yeast-Based Therapeutic Platforms for Alzheimer’s Disease. Academic Journal of Science and Technology, 18(1), 665-670. https://doi.org/10.54097/ebecyp21