Brief description:

Alzheimer’s disease (AD) is a multi-factorial disease that remains an intractable problem in the elderly and no cure exists. Notably, AD affects 35 million people worldwide and is the most common cause of dementia. Thus, accelerating innovation in AD therapeutics is an urgent priority, particularly as current therapies target only 1 aspect of the complex pathology in AD.

In this project, we will characterise an innovative series of polyfunctional agents that: (1)   act as lipophilic transport vehicles to enter the brain and donate a NAD+ precursor upon hydrolysis in acidic lysosomes, facilitating NAD+ biosynthesis and increasing the NAD+/NADH ratio; (2)   promote the function of the NAD+-dependent SIRT signalling that is vital in neurogenesis and non-amyloidogenic APP processing; (3) remove excess redox-active metals to alleviate oxidative stress and prevent APP production. This multifaceted strategy will decrease Aβ levels, Aβ aggregation and senile plaques.