Sirtuin 1 is thought as one of the candidate molecules for promoting healthy aging, because of its neuroprotective roles against several age-related pathologies, and several studies done in animals showed an association between sirtuin 1 and lifespan elongation. Modulation of sirtuin 1 has been shown to impact several aggregate-forming neurodegenerative disorders including Alzheimer?s disease (AD), Parkinson?s disease (PD), Huntington?s disease (HD), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy. Unfortunately, there are no suitable non-invasive imaging tools for investigating these processes in animals or in man. The development of techniques for visualizing sirtuin 1 in vivo represents a key step in understanding both the normal function and pathophysiology of sirtuins in brain. Moreover, these techniques will accelerate the discovery of small molecule therapeutics that interacts with sirtuin 1. The project is designed to develop novel PET imaging probes for sirtuin 1. We will modify the structure of Selisistat, a selective sirtuin 1 inhibitor, labeled with carbon-11 and evaluate its potential to serve as radiotracers for sirtuin 1 in humans by imaging their distribution and pharmacokinetics in rodents and non-human primates.
Sirtuin 1 is thought as one of the candidate molecules for promoting healthy aging and lifespan elongation. However, the relationships between sirtuin 1 density, drug treatment and response are poorly understood. This proposal aims to develop the first in vivo imaging tool for directly probing sirtuin 1 using MR-PET. This will accelerate sirtuin research and the discovery of sirtuin therapeutics, which could be used to treat various human disorders.
