A future treatment for Alzheimer disease may involve a nasal spray. Researchers at Università Cattolica and Fondazione Policlinico Universitario A. Gemelli IRCCS have discovered that by inhibiting the brain enzyme S-acyltransferase (zDHHC) through a nasal-spray drug, they can counteract the cognitive decline and brain damage typical of the disease.

The study has been led by Professor Claudio Grassi, Director of the Neuroscience Department, and Professor Salvatore Fusco, with the collaboration of the University of Catania. The researchers observed that the post-mortem brains of Alzheimer patients contained an excess of S-acyltransferase, which could be a promising therapeutic target of new drugs. They also found that higher concentrations of this enzyme were associated with worse cognitive performance.

Thanks to a €890,000 grant from the Ministry of Health's 2023 PNRR call, new therapeutic approaches against this enzyme will be explored. Background The development of Alzheimer is driven by alterations in certain proteins, including beta-amyloid and tau, which aggregate and accumulate in the brain. These proteins' functions are regulated by multiple signals and modifications, including the attachment of a fatty acid molecule in a biochemical reaction called "S-palmitoylation" , which is performed by S-acyltransferase enzymes (zDHHC).

"In previous studies, we demonstrated that altered S-palmitoylation of synaptic proteins plays a critical role in cognitive decline induced by.