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Exploring the Impact of Synthetic mRNA Vaccines and Pseudouridine on ALS
Synthetic mRNA vaccines use pseudouridine to stabilize RNA and improve protein production, but this chemical modification can subtly affect how ribosomes read codons. These slight misreadings may lead to amino acid misincorporation, producing proteins that are misfolded and prone to aggregation. Misfolded protein aggregates trigger endoplasmic reticulum (ER) stress and chronic activation of the unfolded protein response (UPR), overwhelming the cell’s quality control mechanisms. Motor neurons, with their long axons and high metabolic demand, are especially vulnerable to this stress, which can impair their function and eventually cause cell death. This cascade of events suggests a potential pathway by which synthetic mRNA and pseudouridine could contribute to ALS-like motor neuron dysfunction. Tags: #mRNA #pseudouridine #proteinMisfolding #motorNeurons #ALS #neurodegeneration #ERStress #UPR #aminoAcidMisincorporation #syntheticRNA
Glenn Rosaroso Vale, MT(AMT), MS(IT), MBA
9/10/20252 min read
Understanding Synthetic mRNA Vaccines
The emergence of synthetic mRNA vaccines has marked a significant advancement in medical science. These vaccines leverage the body's own cellular machinery to produce immune responses, offering rapid and effective protection against infectious diseases. Unlike traditional vaccines, synthetic mRNA vaccines can be developed and modified quickly, providing a vital tool in combating viral outbreaks. However, the implications of utilizing modified mRNA, especially concerning sensitive cell types like neurons, necessitates thorough investigation.
The Role of Pseudouridine in mRNA Stability
Pseudouridine (ψ) is a naturally occurring isomer of uridine that is incorporated into tRNA and rRNA, where it plays a crucial role in stabilizing RNA structure. In the context of synthetic mRNA vaccines, pseudouridine is used to enhance mRNA stability and prolong the duration of protein expression, thereby improving vaccine efficacy. By replacing standard uridine residues with pseudouridine, researchers can reduce the immune response to foreign RNA, allowing for smoother cellular processing. This modification provides a unique avenue for optimizing therapeutic potential, including its investigation in neurodegenerative conditions.
Potential Contributions to ALS Research
Amyotrophic lateral sclerosis (ALS) poses significant challenges to researchers due to its complex pathophysiology. Recent studies have begun exploring the intersection between synthetic mRNA technologies and the treatment of ALS. The incorporation of pseudouridine in mRNA strands might not only enhance the stability of therapeutic mRNA but also facilitate targeted delivery to neurons. Given that ALS results in the degeneration of motor neurons, understanding how synthetic mRNA interacts with neuronal cells emerges as a critical research focus. By employing modified mRNA, scientists aim to develop precision therapies that can directly influence neuronal health and function.
Moreover, synthetic mRNA vaccines that utilize pseudouridine may hold promise in educating the immune system about specific neurodegenerative mechanisms, potentially paving the way for innovative therapeutic strategies. As researchers delve deeper into this domain, the hope is that synthetic mRNA technologies can contribute to breakthroughs in our understanding and treatment of ALS.
SOURCE: von Ranke, N., Zhang, W., Anokin, P., Hulscher, N., McKernan, K. J., McCullough, P. A., & Catanzaro, J. A. (2025, July 25). Synthetic mRNA vaccines and transcriptomic dysregulation: Evidence from new-onset adverse events and cancers post-vaccination [Preprint]. Preprints. https://doi.org/10.20944/preprints202507.2155.v1
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