A promising new approach for treating Alzheimer’s disease could involve a nasal spray, according to a study led by researchers at Università Cattolica and Fondazione Policlinico Universitario A. Gemelli IRCCS. By inhibiting a brain enzyme called S-acyltransferase (zDHHC), scientists believe they can slow down cognitive decline and prevent brain damage associated with Alzheimer’s.
The study, led by Professor Claudio Grassi and Professor Salvatore Fusco, has identified the enzyme as a potential target for new drug therapies. Their research, in collaboration with the University of Catania, found that Alzheimer’s patients showed an excess of this enzyme in their brains, which was linked to worse cognitive performance.
The breakthrough study has been supported by an €890,000 grant from the Ministry of Health’s 2023 PNRR program, which will fund further research into potential therapies targeting zDHHC.
Understanding Alzheimer’s and the Role of S-acyltransferase
Alzheimer’s disease is characterized by the buildup of harmful proteins in the brain, including beta-amyloid and tau. These proteins disrupt normal brain function and contribute to cognitive decline. The process of attaching fatty acid molecules to proteins—called S-palmitoylation—is critical in regulating these proteins, and it is carried out by the enzyme S-acyltransferase.
In earlier studies, Professor Fusco’s team demonstrated that changes in S-palmitoylation play a significant role in cognitive decline linked to metabolic diseases such as type 2 diabetes. There is a growing understanding that insulin resistance may also contribute to Alzheimer’s, earning it the nickname “type III diabetes.”
Testing New Treatments
Dr. Francesca Natale, the lead author of the study, noted that in animal models of Alzheimer’s, both genetic and pharmacological inhibition of protein S-palmitoylation could prevent harmful protein buildup in neurons. This, in turn, delayed cognitive decline. The study also found higher levels of the enzyme zDHHC7 and S-palmitoylated proteins in post-mortem brain samples from Alzheimer’s patients. There was an inverse correlation between the presence of these proteins and cognitive function, as measured by the Mini Mental State Examination.
In experiments with genetically modified mice designed to replicate Alzheimer’s disease, researchers used an experimental nasal spray drug called “2-bromopalmitate” to block the zDHHC enzymes. This intervention successfully halted neurodegeneration, reduced symptoms, and even extended the lifespan of the animals.
Looking Ahead: Potential for Human Therapies
Despite the success of the nasal spray in animal models, Professor Grassi cautioned that current drugs do not specifically target the zDHHC7 enzyme. Moreover, while 2-bromopalmitate has shown promise, it is not precise enough for clinical use.
Thanks to the recent funding from the Ministry of Health, researchers will explore new therapeutic options, including the use of “genetic patches” (small molecules that target the RNA of the zDHHC7 enzyme and prevent its activation) and engineered proteins that can directly interfere with zDHHC enzyme activity. These new strategies could eventually lead to more effective treatments for Alzheimer’s in humans.
As research continues, scientists are hopeful that this new line of therapy could offer a breakthrough in the fight against Alzheimer’s disease, a condition that affects millions of people worldwide.
Related topics:
- Study Investigates Genetic Factors Linked to Alzheimer’s Disease Using Cerebrospinal Fluid Proteins
- Researchers Aim To Create Noninvasive Tests For Chronic Fatigue Syndrome
- Study Links Emotion Regulation in Depression to Increased Suicide Risk
