World's Deadliest Protein or the Cure to Neurodegeneration?

Authored by: Evelyn Caputo

Art by: Fiona Reilly

Walking into a room only to forget your reasoning for doing so is truly a universal human experience. After all, memory, while being a very precious part of life, can be extremely fickle. The human brain is one of the most complex organs in the body and, therefore, one of the most heavily studied. As neuroscience research continues to develop, researchers have struggled to discover potential treatments to slow the cognitive decline of patients suffering from diseases such as Alzheimer’s (AD) and Parkinson’s (PD). What if I told you that the world’s deadliest protein could hold the secrets to curing these diseases? Recently, researchers found that the protein assemblies leading to AD and PD can take on multiple self-propagating conformations. These conformations are similar to prions: deadly infectious proteins that spread without the need for DNA or RNA [1]. As a result, prion research offers a unique lens for better understanding and potentially treating neurodegenerative diseases. 

Prions (PrP^C) are a type of infectious protein that can trigger other, normal proteins to fold abnormally (PrP^Sc) and self-propagate [2]. The infectious spread of these proteins ultimately leads to diseases such as Creutzfeldt-Jakob Disease, also known as Mad Cow Disease, and other debilitating prion diseases [2]. Symptoms range from rapid-onset dementia to uncontrollable movements and impaired mobility [2]. Currently, there is no cure for prion diseases, and the only treatment available is palliative care [3]. Additionally, these diseases share key similarities with both Alzheimer’s and Parkinson’s disease, including neurological and motor function symptoms.

The development of Alzheimer’s disease occurs as a result of the misfolding of amyloid-beta (Aβ) and tau proteins [4]. This leads to the formation of amyloid plaques, which disrupt cell function, and tau tangles, which impair synaptic communication between neurons [5]. Similarly, Parkinson’s disease results from the loss of neurons near the brain’s base. The disease is also characterized by the presence of Lewy bodies, aggregates of misfolded alpha-synuclein proteins [6]. Just as prions do, Aβ, tau, and alpha-synuclein proteins adopt abnormal conformations and recruit other proteins to misfold similarly, though they do not spread infectiously across individuals. These diseases all progress through a staging process, in which misfolded proteins accumulate silently during preclinical stages [7]. 

When contrasting these three types of neurodegenerative diseases – prion diseases, Alzheimer’s, and Parkinson’s – it is important to note that prion diseases develop much more rapidly, with patients facing cognitive decline, motor dysfunction, and psychiatric symptoms over the course of weeks or months [3]. On the other hand, patients with Alzheimer’s and Parkinson’s can live for years or even decades with both causing cognitive decline – Alzheimer’s leading to signs of memory loss and personality changes, and Parkinson’s leading to a decline in motor function [8]. 

Given the similar mechanisms across these neurodegenerative diseases and the well-known misfolding mechanisms, prions can be a useful model for researching therapeutic approaches and experimental treatments for AD and PD. Specifically, immunotherapy approaches targeting aggregates of misfolded proteins have the potential to improve treatment outcomes for AD and PD, given their prion-like propagation of toxic proteins [9][10]. In an article published by the National Institutes of Health in 2019, another potential treatment, antisense oligonucleotides (ASOs), was found to extend the survival of prion-infected mice [11]. This discovery has bolstered previous hypotheses that ASOs could lead to the development of treatments for AD and PD [12]. 

While there are some key differences between prion diseases and AD and PD, the unifying connection of self-propagating misfolded proteins across these diseases is extremely important. It outlines the value of cross-disease research and how similarities in symptom structure can lead to similar treatment outcomes. It seems that prions might not just be the world’s deadliest protein but also an unlikely hero, serving as a strong engine for breakthroughs in neurodegenerative disease research. 

References:

1. Das, A. S., & Zou, W.-Q. (2016). Prions: Beyond a single protein. Clinical Microbiology Reviews, 29(3), 633-658. https://doi.org/10.1128/cmr.00046-15

2. Prion Diseases. (n.d.). Johns Hopkins Medicine. Retrieved April 5, 2026, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/prion-diseases

3. Prion Diseases. (2024, January 21). Cleveland Clinic. Retrieved April 6, 2026, from https://my.clevelandclinic.org/health/diseases/prion-disease

4. Zhou, J., & Liu, B. (2013). Alzheimer's disease and prion protein. Intractable & Rare Diseases Research. https://doi.org/10.5582/irdr.2013.v2.2.35

5. What Happens to the Brain in Alzheimer's Disease? (2024, January 19). NIH: National Institute on Aging. Retrieved April 6, 2026, from https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain-alzheimers-disease

6. Parkinson's Disease. (2025, March 5). NIH: National Institute of Neurological Disorders and Stroke. Retrieved April 6, 2026, from https://www.ninds.nih.gov/health-information/disorders/parkinsons-disease

7. Katsuno, M., Sahashi, K., Iguchi, Y., & Hashizume, A. (2018). Preclinical progression of neurodegenerative diseases. Nagoya Journal of Medical Sciences. https://doi.org/10.18999/nagjms.80.3.28 

8. Disease Connections: Alzheimer's and Parkinson's. (2024, February 6). American Brain Foundation. Retrieved April 6, 2026, from https://www.americanbrainfoundation.org/disease-connections-alzheimers-and-parkinsons/#:~:text=However%2C%20each%20disease%20has%20distinct,movement%20and%20fine%20motor%20skills.

9. Valera, E., Spencer, B., & Masliah, E. (2016). Immunotherapeutic approaches targeting amyloid-β, α-Synuclein, and tau for the treatment of neurodegenerative disorders. Neurotherapeutics, 13(1), 179-189. https://doi.org/10.1007/s13311-015-0397-z 

10. Ma, Y., & Ma, J. (2020). Immunotherapy against prion disease. Pathogens, 9(3), 216. https://doi.org/10.3390/pathogens9030216 

11. Raymond, G. J., Zhao, H. T., Race, B., Raymond, L. D., Williams, K., Swayze, E. E., Graffam, S., Le, J., Caron, T., Stathopoulos, J., O'Keefe, R., Lubke, L. L., Reidenbach, A. G., Kraus, A., Schreiber, S. L., Mazur, C., Cabin, D. E., Carroll, J. B., Minikel, E. V., . . . Vallabh, S. M. (2019). Antisense oligonucleotides extend survival of prion-infected mice. JCI Insight, 4(16). https://doi.org/10.1172/jci.insight.131175

12. Bennett, C. F., Kordasiewicz, H. B., & Cleveland, D. W. (2021). Antisense drugs make sense for neurological diseases. Annual Review of Pharmacology and Toxicology, 61(1), 831-852. https://doi.org/10.1146/annurev-pharmtox-010919-023738