Alzheimer’s disease (AD) is a progressive brain disorder and is the leading cause of dementia worldwide. Despite years of research, there is still no cure. New antibody-based treatments targeting amyloid-β (Aβ) have recently emerged, but their efficacy is modest. These treatments are expensive and can cause immune-related side effects, highlighting the urgent need for safer and more affordable options that can slow disease progression.
Recent research published in neurochemistry international It offers amazing possibilities. Researchers at Kindai University and affiliated institutions have discovered that the natural amino acid arginine can reduce the accumulation of harmful Aβ protein in animal models of Alzheimer’s disease. Arginine also acts as a safe chemical chaperone, helping proteins maintain proper structure.
The research team noted that while arginine is widely available as a commercial supplement, the doses and methods used in this study were specifically designed for research purposes and are not the same as commercially available products.
The research group included graduate student Kanako Fujii and professor Yoshitaka Nagai from the Department of Neurology, Kinki University School of Medicine, and associate professor Toshihide Takeuchi from the Kinki University Institute of Life Science.
Laboratory and animal studies have shown strong efficacy
Researchers have shown for the first time in laboratory experiments that arginine can block the formation of Aβ42 aggregates, which are thought to be particularly toxic. The effect increased with higher concentrations.
Next, they tested oral arginine in two established Alzheimer’s disease models.
- Drosophila model expressing Aβ42 with Arctic mutation (E22G)
- Ann AppNL-GF Knock-in mouse model with three familial AD mutations
In both cases, arginine treatment reduced Aβ accumulation and alleviated its deleterious effects.
“Our study demonstrates that arginine can inhibit Aβ aggregation. in vitro and alive“What makes this discovery interesting is that arginine is already known to be clinically safe and inexpensive, making it a very promising candidate for repositioning arginine as a therapeutic option,” Professor Nagai explains.
Improve brain health and reduce inflammation
In mouse models, the benefits go beyond reducing protein accumulation. Arginine lowered amyloid plaque levels and reduced the amount of insoluble Aβ42 in the brain. The treated mice also performed better in behavioral tests.
Researchers found that arginine reduced the activity of genes associated with pro-inflammatory cytokines associated with neuroinflammation, a key feature of Alzheimer’s disease. This suggests that arginine may protect brain cells more broadly than just preventing harmful protein aggregation.
“Our findings open new possibilities to develop arginine-based strategies against neurodegenerative diseases caused by protein misfolding and aggregation,” Professor Nagai points out. “Given its excellent safety profile and low cost, arginine has the potential for rapid application in clinical trials for Alzheimer’s disease and potentially other related diseases.”
A low-cost path to new Alzheimer’s treatments
This study highlights the growing interest in drug repositioning, which involves finding new uses for existing, well-established compounds. Arginine is already in clinical use in Japan and has been shown to reach the brain safely, potentially bypassing some of the early hurdles that slow traditional drug development.
Still, researchers caution that more research is needed. Additional preclinical and clinical studies are needed to determine whether these results can be reproduced in humans and to establish the most effective dosing strategies.
Still, the findings provide strong initial evidence that simple nutritional or pharmacological approaches can help reduce amyloid accumulation and improve brain function.
Expanding our understanding of the biology of Alzheimer’s disease
Beyond its therapeutic potential, this study sheds new light on how Aβ proteins form and accumulate in the brain. It also points to a practical and cost-effective strategy that could ultimately benefit millions of people living with Alzheimer’s disease around the world.
Professor Yoshitaka Nagai, a neurologist and head of the Department of Neurology at Kindai University School of Medicine in Osaka, focuses on researching neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. His research focuses on protein misfolding and RNA-related mechanisms and has received multiple awards from organizations such as the Japanese Society of Neurochemistry and the Japanese Dementia Society.
This research was supported by the Ministry of Education, Culture, Sports, Science and Technology (Project Number: 20H05927), the Japan Society for the Promotion of Science (Project Numbers: 24H00630, 21H02840, 22H02792, 25K02432), and the Japan Science and Technology Agency (JST) Super Highway Project. (SHW2023-03), National Center for Psychiatry and Neurology.
