Article Impact Level: HIGH Data Quality: STRONG Summary of Neurochemistry International https://doi.org/10.1016/j.neuint.2025.106082 Dr. Kanako Fujii et al.
Points
- Researchers evaluated the amino acid arginine as a chemical chaperone to inhibit the aggregation of toxic amyloid beta proteins associated with Alzheimer’s disease pathology.
- In vitro experiments demonstrated that arginine treatments effectively inhibited the formation of amyloid beta 42 aggregates in a concentration-dependent manner without cytotoxicity.
- Oral administration in Drosophila models expressing the Arctic mutation resulted in a dose-dependent reduction of protein accumulation and a rescue of toxicity phenotypes.
- Tests on AppNL-G-F knock-in mice revealed that the treatment significantly decreased amyloid plaque deposition and lowered levels of insoluble amyloid beta in the brain.
- The treated mice exhibited improved behavioral outcomes and reduced expression of pro-inflammatory cytokine genes indicating broad neuroprotective effects beyond simple aggregation inhibition.
Summary
This study investigated the therapeutic potential of arginine, a naturally occurring amino acid and chemical chaperone, in suppressing amyloid β (Aβ) aggregation for Alzheimer’s disease (AD) treatment. Given the limited efficacy and adverse effect profiles of current antibody-based therapies, the researchers assessed whether oral arginine administration could mitigate Aβ pathology. In vitro assays demonstrated that arginine inhibits Aβ42 aggregate formation in a concentration-dependent manner, prompting further evaluation in in vivo models to test safety and brain permeability.
Using a Drosophila model expressing Aβ42 with the Arctic mutation (E22G), the study found that oral administration yielded a dose-dependent reduction in Aβ42 accumulation and rescued Aβ-mediated toxicity. Subsequent testing in AppNL-G-F knock-in mice, which harbor three familial AD mutations, revealed that arginine significantly decreased amyloid plaque deposition and levels of insoluble Aβ42 within the brain. Furthermore, the treated mice exhibited improvements in behavioral performance compared to untreated controls.
The study also noted a reduction in the expression of genes encoding pro-inflammatory cytokines, suggesting a neuroprotective mechanism extending beyond simple aggregation inhibition. These findings indicate that arginine effectively ameliorates Aβ-mediated neurological phenotypes and suppresses neuroinflammation. As a clinically approved compound with a known safety profile, arginine represents a promising candidate for drug repositioning strategies in AD and other protein misfolding disorders, though human clinical trials are required to establish optimal dosing.
Link to the article: https://www.sciencedirect.com/science/article/pii/S019701862500155X?via%3Dihub
References
Fujii, K., Takeuchi, T., Fujino, Y., Tanaka, N., Fujino, N., Takeda, A., Minakawa, E. N., & Nagai, Y. (2025). Oral administration of arginine suppresses Aβ pathology in animal models of Alzheimer’s disease. Neurochemistry International, 191, 106082. https://doi.org/10.1016/j.neuint.2025.106082
