A study by the Institute for Bioengineering of Catalonia (IBEC) and Northwestern University (USA), published Wednesday in the Journal of the American Chemical Society, reported on a novel nanotherapy to combat neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis (ALS). This therapy is based on trehalose, a natural sugar derived from plants.
According to the article, this nanotherapy captures and neutralizes toxic proteins to halt the progression of the disease. This prevents the harmful proteins from entering neurons and causing damage.
Misfolded Proteins and Cell Death
In severe neurodegenerative diseases such as Alzheimer’s disease and ALS, certain proteins with structural defects accumulate around neuronal cells in the brain and spinal cord, ultimately leading to cell death.
The new treatment effectively captures these proteins before they can aggregate into toxic structures capable of penetrating neurons. Once the proteins are encapsulated, they are degraded without causing harm to the body.
This “cleaning” strategy was tested on laboratory-grown human neurons exposed to the stress of pathogenic proteins. The results showed a significant increase in cell survival.
Samuel I. Stupp, one of the study’s lead authors from Northwestern University, emphasizes that the research “demonstrates the exciting potential of molecularly engineered nanomaterials to study the origin of neurodegenerative diseases.”
Preventing Toxic Aggregates
In many of these diseases, proteins lose their functional, correctly folded structure and aggregate into destructive fibers that invade neurons and are highly toxic.
The new treatment works by capturing misfolded proteins and preventing them from forming toxic aggregates at an early stage. This includes blocking the formation of soluble oligomers and short amyloid fibers, which are known to penetrate neurons and cause significant damage.
Zaida Alvarez, senior researcher in the Biomaterials for Neuronal Regeneration group at IBEC and co-author of the study, believes that with continued research, this approach “could significantly slow the progression of the disease.”
According to the World Health Organization (WHO), up to 50 million people worldwide may suffer from a neurodegenerative disease. Most of these diseases are characterized by the accumulation of misfolded proteins in the brain, leading to progressive neuronal loss.
Although current treatments offer limited relief, there is a critical need for new therapies. To address this challenge, the researchers turned to a class of amphiphilic peptides—molecules with one hydrophilic and one hydrophobic end that contain modified chains of amino acids.
The molecules in this novel therapeutic concept are broken down into harmless lipids, amino acids, and sugars, resulting in fewer unwanted side effects.
A Sugary Solution
To develop an amphiphilic peptide for the treatment of neurodegenerative diseases, the research team added an additional ingredient: the natural plant sugar trehalose.
“Trehalose occurs naturally in plants, fungi, and insects,” explains the study’s lead author, Zijun Gao, “and protects these organisms from temperature fluctuations, especially desiccation and freezing.”
The researchers believe that the novel method of using unstable trehalose-coated nanofibers for protein binding represents a promising approach for developing new and effective therapies for Alzheimer’s disease, ALS, and other neurodegenerative diseases.
Similar to cancer treatments that combine various therapies such as chemotherapy, surgery, hormone therapy, and radiation, nanotherapy could be most effective when combined with other treatments.
References:
Zijun Gao, Ruomeng Qiu, Dhwanit R. Dave, Palash Chandravanshi, Gisele P. Soares, Cara S. Smith, J. Alberto Ortega, Liam C. Palmer, Zaida Alvarez, Samuel I. Stupp. Supramolecular copolymerization of glycopeptide amphiphiles and amyloid peptides enhances neuronal survival. Journal of the American Chemical Society (2025). https://pubs.acs.org/doi/10.1021/jacs.5c00105.
